JP2003000270A - Tumor antigen - Google Patents

Abstract

PROBLEM TO BE SOLVED: To find out a molecule (a tumor antigen) to be recognized by a cytotoxic T-cell, from a cell strain originated from human lung cancer. SOLUTION: An HLA-A24 restrictive tumor-specific cytotoxic T-cell (GK-CTL) which recognizes HLA-A24 and a tumor antigen peptide and is activated therewith is established from a human lung cancer patient. A gene encoding the tumor antigen capable of being recognized by the tumor-specific cytotoxic T-cell is isolated and identified from the cDNA library of human lung cancer- originated cell strain 11-18 by a gene expression cloning method. Further, a peptide having the epitope of the tumor antigen is found out on the basis of the tumor antigen encoded in the obtained gene.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a novel tumor antigen, and more specifically to a peptide recognized by a tumor-specific cytotoxic T cell, a polynucleotide encoding the peptide or a complementary strand thereof, the polynucleotide or Recombinant vector containing the complementary chain, transformant containing the recombinant vector, antibody to the peptide, compound interacting with the peptide or the polynucleotide or its complementary chain, cytotoxic T-containing peptide Cell inducers, pharmaceutical compositions containing one or more of these,
Method for producing the peptide, method for identifying a compound that interacts with the peptide or the polynucleotide or a complementary chain thereof, method for inducing cytotoxic T cells using the peptide, polypeptide encoding the peptide or the peptide The present invention relates to a method for measuring nucleotides and a reagent kit used for the identification method or the measurement method.

[0002]

2. Description of the Related Art In order to eliminate cancer in the living body, the immune system, especially cytotoxic T cells (Cytotoxic T Lymp) is used.
hockey) plays an important role. Infiltration of cytotoxic T cells showing a cytotoxic activity against tumor cells has been observed in the tumor local areas of cancer patients (Arch. Sur.
g. 126: 200-205, 1990). The target molecule (tumor antigen) of this tumor-specific cytotoxic T cell is
First discovered in melanoma. Tumor antigens produced in tumor cells are decomposed intracellularly to peptides (tumor antigen peptides) consisting of 8 to 11 amino acids, and human leukocyte antigen (HL) which is a major histocompatibility antigen.
A) Presented on the surface of tumor cells in association with molecules. Cytotoxic T cells recognize a complex composed of HLA and a tumor antigen peptide and damage tumor cells. That is, cytotoxic T cells recognize tumor cells in an HLA-restricted manner.

HLA is a cell membrane antigen and is expressed on almost all nucleated cells. HLA is roughly classified into class I antigen and class II antigen, and HLA recognized together with an antigen peptide by cytotoxic T cells is a class I antigen. HLA class I antigens are further identified as HLA-A,
In humans, nucleated cells are classified into AB, HLA-C, etc., and have different amounts of HLA-A, HLA-B, or HLA-C. In addition, it has been reported that the gene is rich in polymorphism. For example, A for HLA-A
Cw for HLA-C, such as B8, B27, and B46 for HLA-B, such as 1, A2, A24, and A26.
There are polymorphisms such as 3 and Cw6. Therefore, the type of HLA that each human has is not necessarily the same. When cytotoxic T cells recognize the complex of HLA class I antigen and tumor antigen peptide, they also recognize the HLA type. Furthermore, it is known that an antigen peptide capable of binding to HLA has a motif (regular sequence) in its sequence for each HLA type.

In recent years, many genes encoding tumor antigens recognized by cytotoxic T cells have been identified from human cancer cell cDNAs (Science, 25).
4: 1643-1647, 1991) (J. Exp. M.
ed. , 183: 1185-1192, 1996).
(J. Immunol., 163: 4994-500.
4, 1999). For example, HER / neu (Proc.
Natl. Acad. Sci. USA, 92: 432.
436, 1995), the mutation cdk (Science, 2)
69: 1281-1284, 1995), and mutation C
ASP-8 (J. Exp. Med., 186: 785.
793, 1997) and the like, which are included in proliferating cells and malignant transformants.

Molecules involved in specific immunity including the tumor rejection antigen gene and T cell antigen receptor (TCR) have been identified in the past 10 years in melanoma, esophageal cancer, and other cancers, and have advanced. Specific immunotherapy with peptides has been investigated in cancer or metastatic cancer.

[0006] Currently, in Europe and the United States, the development of a cancer vaccine therapy which activates cytotoxic T cells in the body of a cancer patient by administering a tumor antigen peptide, has been successful in clinical trials for melanoma-specific tumor antigens. It has been reported. For example, melanoma antigen gp100 peptide was subcutaneously administered to melanoma patients, and interleukin-
By administration of 2 (IL-2) intravenously, 42%
Shrinkage has been observed in some patients (Nature
Medicine, 4: 321, 1998). Thus, when a tumor antigen is used as a vaccine, an effective cancer treatment effect can be expected.

However, many of the identified tumor antigens are derived from melanoma, and there are few reports on tumor antigens derived from epithelial cancer or adenocarcinoma with a high incidence of disease. Further, considering the diversity of cancers, it is not considered that the same tumor antigen is expressed to the same extent in all cancer cells.
Of course, a cancer vaccine therapy in which a single tumor antigen is used to activate cytotoxic T cells can also provide a therapeutic effect on cancer having the tumor antigen. However, in order to induce specific cytotoxic T cells in the treatment of cancer and to obtain a high therapeutic effect in response to the diversity of cancer, many new tumor antigens corresponding to the diversity of cancer are used. It is important to discover and use it.

[0008]

The problem to be solved by the present invention relates to cytotoxic T cells useful for specific immunotherapy of patients with adenocarcinoma and epithelial cancer such as colon cancer and lung cancer. To find and provide a novel tumor antigen that is recognized.

Specifically, it is to provide a peptide recognized by at least HLA-A24-restricted cytotoxic T cells. More specifically, a peptide recognized by an HLA-A24-restricted cytotoxic T cell, a polynucleotide encoding the peptide or a complementary chain thereof, a recombinant vector containing the polynucleotide or a complementary chain thereof, the recombinant vector , An antibody against the peptide, a compound that interacts with the peptide or the polynucleotide or a complementary chain thereof, an inducer of cytotoxic T cells comprising the peptide, and a pharmaceutical composition containing one or more of these Product, a method for producing the peptide, a method for identifying a compound that interacts with the peptide or the polynucleotide or a complementary chain thereof, a method for inducing a cytotoxic T cell using the peptide, the peptide or the peptide encoding Method for measuring existing polynucleotide, and the identifying method or the measuring method To provide a reagent kit for use in.

[0010]

[Means for Solving the Problems] The present inventors have found that HLA-A2
Which is activated by recognizing 4 and tumor antigen peptides
-A24-restricted tumor-specific cytotoxic T cells (GK-C
TL is a tumor infiltrating lymphocyte (Tumo) derived from a lung cancer patient.
ur-Infiltrating Lymphocyt
e) a gene established from (TIL) and encoding a tumor antigen that can be recognized by this tumor-specific cytotoxic T cell,
CDNA of human lung adenocarcinoma cell line 11-18 (HLA-A2402 / 0201) using gene expression cloning method
The present invention was completed by isolating and identifying from the A library, and further, based on the tumor antigen encoded by the obtained gene, a peptide having an epitope of the tumor antigen was found.

That is, the present invention includes (1) a peptide consisting of the amino acid sequence set forth in any one of SEQ ID NO: 1 to SEQ ID NO: 766 in the sequence listing; (3) SEQ ID NO: 1 in the sequence listing, which is a drug comprising a peptide consisting of the amino acid sequence described in 1.
To (4) a cancer vaccine containing a peptide consisting of the amino acid sequence of SEQ ID NO: 766, (4) the pharmaceutical or cancer vaccine of (2) or (3) above, which is used for the treatment of lung cancer or renal cancer, (5) A cytotoxic T cell inducer containing a peptide consisting of the amino acid sequence of any one of SEQ ID NO: 1 to SEQ ID NO: 766 in the sequence listing, (6)
A method for inducing cytotoxic T cells, which comprises using the peptide consisting of the amino acid sequence set forth in any one of SEQ ID NO: 1 to SEQ ID NO: 766 in the sequence listing, (7) Sequences from SEQ ID NO: 1 in the sequence listing A polynucleotide encoding a peptide consisting of the amino acid sequence of any one of SEQ ID NO: 766 or its complementary strand, (8) a peptide consisting of the amino acid sequence of any one of SEQ ID NO: 1 to SEQ ID NO: 766 in the sequence listing, A polynucleotide encoding the polynucleotide according to any one of SEQ ID NO: 767 to SEQ ID NO: 774 in the sequence listing or a complementary strand thereof,
(9) Any one of SEQ ID NO: 767 to SEQ ID NO: 774
The polynucleotide or the complementary chain thereof, wherein the polypeptide encoded by the polynucleotide induces cytotoxic T cells and / or is recognized by the cytotoxic T cells, (10) A polynucleotide which hybridizes with the polynucleotide according to any one of (7) to (9) or a complementary strand thereof under stringent conditions, (11) above (7)
To (10) the recombinant vector containing the polynucleotide or a complementary strand thereof, (12) the recombinant vector of (11) above, wherein the recombinant vector is an expression recombinant vector, (13) the above (11) Or (14) a transformant obtained by introducing the recombinant vector, (14) a step of culturing the transformant obtained by introducing the recombinant vector of (12), Manufacturing method, (15) An antibody that immunologically recognizes the peptide of (1), (16) At least HLA-A2 by interacting with the peptide of (1) and / or HLA-A24.
A compound that enhances the recognition of the peptide by 4-restricted cytotoxic T cells, and / or (7) to (10) above
A method for identifying a compound that interacts with any of the polynucleotides or their complementary strands to enhance its expression, comprising the peptide of (1) above, the polynucleotide of any one of (7) to (10) above, or Its complementary strand, the recombinant vector of (11) or (12) above,
3) A transformant or at least one of the antibodies of (15) above is used, (1)
7) A compound obtained by the method according to the above (16), (1
8) H for at least one of the peptides of (1) above
A compound that enhances the recognition by LA-A24-restricted cytotoxic T cells, or a compound that interacts with the polynucleotide of any one of (7) to (10) above or its complementary strand to enhance its expression, (19 ) The peptide according to (1) above, the polynucleotide according to any one of (7) to (10) above or a complementary strand thereof, (11) or (12) above
A recombinant vector, a transformant according to (13), an antibody according to (15), and at least one of the compounds according to (17) or (18), which is used for cancer treatment. Pharmaceutical composition, (20) A method for quantitatively or qualitatively measuring the peptide of (1) above or the polynucleotide of any of (7) to (10) above, (21) above (16) or (20) A reagent kit for use in the method of claim 1, which comprises the peptide of (1) above, the polynucleotide of any of (7) to (10) above, the recombinant vector of (11) or (12) above, (13) above. Or a reagent kit containing at least one or more of the antibody of (15) above.

[0012]

BEST MODE FOR CARRYING OUT THE INVENTION (Identification of Tumor Antigen Gene) The present inventors recognized HLA-A24, which is a type of HLA-A molecule found in many Japanese and tumor antigen peptide, and were activated. HLA-A24-restricted tumor-specific cytotoxic T cells were previously reported (J. Immunol., 16
3: 4994-5004, 1999),
Tumor-infiltrating lymphocytes derived from lung cancer patients (Tumour-In
filtering Lymphocyto) (TI
Established from L). Hereinafter, this cell is referred to as GK-CTL. A gene encoding a tumor antigen that can be recognized by this GK-CTL was cloned into a human lung cancer cell line 11-18 cells (HLA-A240) using a gene expression cloning method.
It was isolated and identified from the cDNA library of 2/0201). Furthermore, based on the tumor antigen encoded by the obtained gene, a peptide having an epitope of the tumor antigen was found.

The term "peptide" as used herein means a substance containing two or more amino acids bound to each other by a peptide bond or a modified peptide bond, and includes proteins, polypeptides, oligopeptides and the like. . Hereinafter, when an amino acid sequence is represented, it may be represented by one letter or three letters.

The tumor antigen means a protein, polypeptide or peptide possessed by a tumor cell which can be recognized by and / or induce a cytotoxic T cell specific to a tumor. The tumor antigen peptide is a peptide generated by the decomposition of the tumor antigen in tumor cells and is recognized by cytotoxic T cells by being bound to HLA molecules and presented on the cell surface.
Or, it means a peptide capable of inducing cytotoxic T cells. Further, a site of an amino acid sequence which is recognized by a tumor-specific cytotoxic T cell and / or can induce a cytotoxic T cell possessed by a tumor antigen is referred to as a tumor antigen epitope (tumor antigen determinant).

Here, "recognize (recognize
By "e)" is meant that the recognizer recognizes the recognized object as distinct from the others and, for example, binds to the recognized object. In particular, herein, cytotoxic T
A cell (hereinafter sometimes abbreviated as CTL) recognizes that the CTL is H
It means to bind to the tumor antigen peptide presented by LA through the T cell receptor. "Activate" means that something or a state having an activity or action is
Means to further enhance or activate. In particular, in this specification, activation of CTL means CT
L recognizes the antigen presented by HLA to produce, for example, IFN-γ, or CTL
Means that the target cell recognized by is cytotoxic. “Induce” means to cause an activity or an action from a substance or a state having little activity or action. In particular, in this specification, inducing antigen-specific CTL means differentiating and / or proliferating CTL that specifically recognizes an antigen in vitro or in vivo. The term "cytotoxic T cell inducer" used herein means a cell that recognizes an antigen from the state in which CD8 positive T cells that specifically recognize the antigen do not exist or are present at a very low ratio. It means a drug that has an effect of changing into a state in which a very large proportion of damaging T cells are present.

(Isolation / Identification of Tumor Antigen Gene) The isolation / identification of the gene encoding the tumor antigen according to the present invention can be carried out by using c of 11-18 cells as described in detail in Examples below.
The DNA was co-transfected with HLA-A2402 cDNA into COS-7 cells, and cells that promote the IFN-γ production from GK-CTL were selected from cells expressing the transgene. As a result, GK-CT
Seven types of cDNA clones encoding a gene product recognized by L under HLA-A24 restriction, that is, clone 5, clone 114, clone 50, clone 8
3, clone 111, clone 96, and clone 1
22 was obtained.

The nucleotide sequence of the obtained cDNA clone was determined by the dideoxynucleotide sequencing method. Regarding clone 114, clone 19-5-114 partially homologous to its nucleotide sequence was obtained. These base sequences are shown in the sequence listing under SEQ ID NO: 767.
~ 774 (see Table 1 below). When a homology search was performed on these nucleotide sequences in an existing database such as GenBank, they were cDNAs having novel nucleotide sequences, although they were homologous to the genes shown below. Although the nucleotide sequence and the deduced amino acid sequence of the human-derived gene found with high homology are disclosed, there is no report that they encode a tumor antigen.

The base sequence of clone 5 is GenBank.
(Accession number: Y17151, AF10494
3, AF085692, AF085690, AF009
670, NM_003786) registered in MRP3 gene (Multidrug Resistance-as).
High homology was observed with that of the sociated Protein 3). The MRP3 gene is ABC (AT
P-binding cassette) transporter, and its function has been reported to be involved in multidrug resistance.

The base sequence of clone 114 is GenBa
Clone 2502, a gene of unknown function, registered in nk with accession number: AF131846
8 was partially homologous. Clone 114 is 3
It consists of 648 bp base, and the base sequence on the 3'side is A
It is homologous to the 197th to 1676th base sequences of F131846, but has no homology to other base sequences. In addition, the nucleotide sequence No. 18 of clone 19-5-114
The 5th and subsequent nucleotides are homologous to the 2861st and subsequent nucleotide sequences of clone 114 and the 907th to 1676th nucleotide sequences of AF131846, but the 1st to 184th nucleotides have no homology with these. Therefore, the clone 114 and the clone 19-5-114 were selected from alternative splicing variants (alternative splice).
ing variant) or another gene of the same family.

The base sequence of clone 50 is GenBan.
High homology was recognized with that of KIAA4184 (human cDNA FLJ20386fis), a gene of unknown function, registered in k (accession number: AK000393). However, clone 50 may have polymorphisms and mutations.

The base sequence of clone 83 is GenBan.
Homology was recognized with Fe65L2, which is a gene of unknown function, registered as accession number: AB024745 in k. Clone 83 consists of 4200 bp bases, and the 158th to 566th base sequences are AB
Although it was homologous to the first to 409th base sequences of 024745, no homology was observed with other base sequences.

The base sequence of clone 111 is GenBa
Accession number to nk: AF093250, AJ1
P38IP (p38 interacting Pr), a gene of unknown function, registered as 30894
homology was observed. Clone 1
11 consists of 2952 bp bases, and the 8th to 579th base sequences are the 38th base sequence of AJ130894.
Although it is homologous to the 1st to 854th nucleotides, no homology was observed with other nucleotide sequences.

The nucleotide sequence of clone 96 is GenBan.
k (accession number: NM_006527, Z71
188) registered HBP gene (Hairpin-
Binding Protein, histone). The HBP gene has been reported as an RNA-binding protein involved in processing of a histone mRNA precursor, but has not been reported as a tumor antigen.

Clone 122 is GenBank (accession number: NM_006007, AF06234).
7, Z06N with unknown function registered in AF062346)
216 genes (Zinc Finger Protei
n 216), a novel alternative splicing variant (al
ternary splicing varian
t). The clone 122 consists of 2004 bp bases, and the 232nd to 2004th base sequences are NM.
_006007 is the same as the 653rd to 2425th nucleotides, but the 5′-terminal nucleotide sequence is different.

Clone 5, clone 114, clone 19-5-114, clone 50, clone 83,
Clone 111, Clone 96, and Clone 122
May be referred to as gene 1, gene 2, gene 3, gene 4, gene 5, gene 6, gene 7, and gene 8, respectively. The gene products of genes 1-8 are called gene products 1-8, respectively.

These eight genes are genes encoding tumor antigens, and when expressed in cells as described above, H
Recognized by LA-A24-restricted CTL,
Can be activated. The amino acid sequences encoded by each of these genes were estimated for all the open reading frames of frame 1 (FL1), frame 2 (FL2), and frame 3 (FL3) for each gene. The resulting peptide consisting of 5 or more amino acids was used as FL1, FL2, and F.
For L3, clone 5 is SEQ ID NO: 18-24, SEQ ID NO: 25-79, and SEQ ID NO: 80 in the sequence listing, respectively.
~ 117; clone 114 is SEQ ID NO: 118 in the sequence listing
175, SEQ ID NOS: 176-232, and SEQ ID NO: 23
Clone 19-5-114 is SEQ ID NO: 290-304, SEQ ID NO: 305-321, and SEQ ID NO: 322-332; Clone 50 is SEQ ID NO: 333-344, SEQ ID NO: 345-350. , And SEQ ID NOS: 351-365; clone 83 is SEQ ID NOS: 366-406, SEQ ID NOS: 407-437, and SEQ ID NOS: 438-479; clone 111 is SEQ ID NOS: 480-529, SEQ ID NOS: 530-572. , And SEQ ID NOS: 573-611; clone 96 is SEQ ID NOS: 612-631, SEQ ID NOS: 632-663, and SEQ ID NOS: 664-675; and clone 122 is SEQ ID NOS: 676-702, SEQ ID NO: 703- 73
2, and SEQ ID NOS: 733-766;

(Identification of Tumor Antigen Peptide) In order to obtain a tumor antigen peptide from the above gene encoding a tumor antigen, the amino acid sequences encoded by the above genes 1 to 8 and MRP3, HBP having high homology with the above gene,
Peptides were synthesized based on the amino acid sequence of the gene product of ZFN and ZFN. It is known that a tumor antigen peptide capable of binding to HLA has a motif (regular sequence) in its amino acid sequence depending on each type of HLA. Therefore, a peptide that can bind to HLA-A24 has been previously reported [Kawano K. et al. , Cancer
Res. 60: 3550-3558 (2000)] [I
be M. et al. , Immunogenetic
s 44: 233-241 (1996)], a 9-mer or 10-mer peptide was designed and synthesized.

Each of the synthesized peptides was used as HLA-A240.
C1R cells into which 2 is introduced into a gene are pulsed, this cell and GK-CTL are co-cultured to measure IFN-γ produced from the GK-CTL, and GK-C is used as an index.
Selection of peptides recognized by TL was performed. Among the synthesized peptides, 17 kinds of peptides (SEQ ID NOS: 1 to 17 in Sequence Listing) (Table 1) were recognized by GK-CTL and promoted IFN-γ production of GK-CTL. GK-
Among the above 17 kinds of peptides recognized by CTL, CTL activation was performed for 4 kinds of peptides derived from MRP3, 1 kind derived from clone 114, 1 kind derived from clone 19-5-114, and 2 kinds derived from clone 50. When the dose-dependence of the action was examined, all were dose-dependently recognized by GK-CTL, and the IF of GK-CTL was recognized.
Promoted N-γ production. In addition, four types derived from MRP3,
CTL from peripheral blood mononuclear cells obtained from a cancer patient for two kinds of clone 114-derived, two kinds derived from clone 50, two kinds derived from clone 83, one kind derived from clone 111, and one kind derived from clone 96 It was investigated whether these peptides could induce target cells from peripheral blood mononuclear cells obtained from cancer patients to promote IFN-γ production and damage the target cells. Inducible CTL were induced in vitro. That is, in the present invention, 17 types of tumor antigen peptides capable of inducing and / or activating HLA-A24-restricted CTL could be obtained. Furthermore, MRP
It was found that the recognition of target cells by the CTL induced by the peptide derived from 3 is related to the expression of MRP3 in the target cells, and the CTL specifically recognizes the peptide used for the induction of the CTL. It was confirmed that the tumor cells expressing the peptide were damaged.

[0029]

[Table 1]

(Peptide) The peptides according to the present invention are the above genes 1 to 8 obtained from the human lung cancer cell line 11-18.
1 is a peptide encoded by the amino acid sequence of SEQ ID NO: 1 to 766, more preferably the amino acid sequence of SEQ ID NO: 1 to 17 of the sequence listing. These peptides are HLA
Since it is recognized by A24-restricted antigen-specific CTL, it can be used as a tumor antigen that induces and / or activates the CTL. In addition, these peptides can be used as a material for identifying a tumor antigen epitope and obtaining a tumor antigen peptide. For example, it can be obtained by designing, for example, those that match the HLA-A24 binding motif based on the amino acid sequences of these peptides, and selecting those that are recognized by HLA-A24-restricted CTL from the designed peptides. . The peptide is HLA-A
Is presented on the surface of antigen-presenting cells by binding to 24, and C
Any peptide having a property as a tumor antigen epitope recognized by TL may be used, and it is a peptide consisting of at least about 5 or more, preferably about 7 or more, and more preferably 9 to 10 amino acid residues. Particularly preferred is a peptide consisting of the amino acid sequence set forth in any one of SEQ ID NOS: 1 to 17 in the sequence listing.

The peptide consisting of the amino acid sequence set forth in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4 is the peptide encoded by FL1 of clone 5, and is SEQ ID NO: 18 in the sequence listing. It is contained in the peptide having the amino acid sequence described in 1. Sequence number 5 in the sequence listing
The peptide consisting of the amino acid sequence described in 1. is clone 1
This is a peptide encoded by FL2 of 14 and included in the peptide consisting of the amino acid sequence set forth in SEQ ID NO: 230 in the sequence listing. The peptide consisting of the amino acid sequence set forth in SEQ ID NO: 6 of the Sequence Listing is a peptide encoded by FL3 of clone 19-5-114, and is included in the peptide consisting of the amino acid sequence set forth in SEQ ID NO: 322 of the Sequence Listing. There is. The peptide consisting of the amino acid sequence set forth in SEQ ID NO: 7 or SEQ ID NO: 8 in the sequence listing is the peptide encoded by FL1 or FL2 of clone 50, respectively, and the amino acid sequence set forth in SEQ ID NO: 344 or SEQ ID NO: 347 in the sequence listing. It is contained in the peptide consisting of. The peptide comprising the amino acid sequence set forth in SEQ ID NO: 9 or 10 in the sequence listing is the peptide encoded by FL2 of clone 83, and is included in the peptide comprising the amino acid sequence set forth in SEQ ID NO: 427 in the sequence listing. . The peptide consisting of the amino acid sequence set forth in SEQ ID NO: 11 or SEQ ID NO: 12 of the sequence listing is a peptide encoded by FL3 of clone 83, and is included in the peptide consisting of the amino acid sequence set forth in SEQ ID NO: 447 of the sequence listing. There is. The peptide consisting of the amino acid sequence set forth in SEQ ID NO: 13 of the sequence listing is a peptide encoded by FL3 of clone 111, and is included in the peptide consisting of the amino acid sequence set forth in SEQ ID NO: 606 of the sequence listing. Sequence number 1 in the sequence listing
4 or the peptide consisting of the amino acid sequence of SEQ ID NO: 15 is a peptide encoded by FL3 of clone 96, and is included in the peptide consisting of the amino acid sequence of SEQ ID NO: 668 in the sequence listing. The peptide consisting of the amino acid sequence set forth in SEQ ID NO: 17 of the sequence listing is a peptide encoded by FL3 of clone 122, and is included in the peptide consisting of the amino acid sequence set forth in SEQ ID NO: 737 of the sequence listing. Therefore, SEQ ID NO: 1 in the sequence listing
8, SEQ ID NO: 230, SEQ ID NO: 322, SEQ ID NO: 34
4, SEQ ID NO: 347, SEQ ID NO: 427, SEQ ID NO: 44
The peptide consisting of the amino acid sequence set forth in SEQ ID NO: 7, SEQ ID NO: 606, SEQ ID NO: 668, or SEQ ID NO: 737 is also recognized as a tumor antigen by HLA-A24-restricted CTL, and therefore for the induction and / or activation of the CTL. Can be preferably used. Further, the peptide consisting of the amino acid sequence set forth in SEQ ID NO: 16 of the Sequence Listing is a known gene ZF.
Although it is a peptide derived from the gene product of N216, there is no report that this peptide is a tumor antigen peptide recognized by HLA-A24-restricted CTL.

The above peptides may be used alone or in combination of two or more for inducing and / or activating CTL. CTLs that are activated by recognizing tumor antigens are considered to be a population of cells that recognize multiple tumor antigens. For example, the above GK-CT
Multiple GK-CTL obtained from L by limiting dilution method
The sublines differed in the degree of recognition of COS-7 cells expressing each of the above 7 types of cDNA clones (see Example 3 and Table 2). In this way, CT
Since L is a plurality of cell populations that recognize various antigens, it is recommended to use two or more of the above peptides in combination.

In addition, 1 is added to the peptide thus identified.
It has a mutation such as deletion, substitution, addition or insertion of one to several amino acids, which is at least HLA-
Peptides recognized by A24-restricted CTL are also included in the scope of the present invention. Means for introducing mutations such as deletion, substitution, addition, or insertion are known per se, and for example, the technique of Ulmer (Science, 219: 666, 198).
3) can be used. In introducing such a mutation, from the viewpoint of not changing the basic properties (physical properties, activity, immunological activity, etc.) of the peptide, for example, a cognate amino acid (polar amino acid, nonpolar amino acid, hydrophobic amino acid, Mutual substitutions between hydrophilic amino acids, positively charged amino acids, negatively charged amino acids, aromatic amino acids, etc.) are readily envisioned. Furthermore, these available peptides are
Modifications such as modification of the constituent amino group or carboxyl group are possible without causing a significant change in function.

(Polynucleotide) The polynucleotide according to the present invention is the above genes 1 to 8 obtained from the human lung cancer cell line 11-18, which are SEQ ID NOs: 767 to
774 is a polynucleotide consisting of the nucleotide sequence described in any one of 774 or its complementary strand. Sequence number 7 in the sequence listing
The polynucleotide consisting of the nucleotide sequence set forth in 67 is SEQ ID NOs: 18 to 24 (FL1) and SEQ ID NOs: 25 to 7 in the sequence listing.
9 (FL2), and SEQ ID NOs: 80 to 117 (FL3).
Which encodes a peptide consisting of the amino acid sequence described in any one of 1. The polynucleotide consisting of the nucleotide sequence set forth in SEQ ID NO: 768 in Sequence Listing is SEQ ID NO: 11 in Sequence Listing.
8 to 175 (FL1), SEQ ID NOS: 176 to 232 (FL
2) and a peptide consisting of the amino acid sequence of any one of SEQ ID NOs: 233 to 289 (FL3). The polynucleotide consisting of the nucleotide sequence set forth in SEQ ID NO: 769 of the Sequence Listing is SEQ ID NO: 290 to 3 of the Sequence Listing.
04 (FL1), SEQ ID NOs: 305 to 321 (FL2),
And any one of SEQ ID NOS: 322 to 332 (FL3)
It encodes a peptide consisting of the amino acid sequence described in 1. The polynucleotide consisting of the nucleotide sequence set forth in SEQ ID NO: 770 of the Sequence Listing is SEQ ID NO: 333-344 of the Sequence Listing.
(FL1), SEQ ID NOS: 345 to 350 (FL2), and SEQ ID NOS: 351 to 365 (FL3), which encodes a peptide consisting of the amino acid sequence of any one of them.
The polynucleotide consisting of the nucleotide sequence set forth in SEQ ID NO: 771 of the Sequence Listing is SEQ ID NO: 366 to 406 (FL
1), SEQ ID NOS: 407 to 437 (FL2), and SEQ ID NOS: 438 to 479 (FL3), which encodes a peptide consisting of the amino acid sequence of any one of them. The polynucleotide consisting of the nucleotide sequence set forth in SEQ ID NO: 772 of the Sequence Listing is SEQ ID NO: 480 to 529 (FL1) in the Sequence Listing,
SEQ ID NOs: 530-572 (FL2), and SEQ ID NO: 5
73 to 611 (FL3), which encodes a peptide consisting of the amino acid sequence described in any one of them. The polynucleotide consisting of the nucleotide sequence set forth in SEQ ID NO: 773 of the Sequence Listing is SEQ ID NO: 612-631 (FL1), SEQ ID NO: 632-663 (FL2), and SEQ ID NO: 664-
675 (FL3), which encodes a peptide consisting of the amino acid sequence described in any one of them. Sequence number 7 in the sequence listing
The polynucleotide consisting of the nucleotide sequence set forth in 74 is SEQ ID NO: 676 to 702 (FL1), SEQ ID NO: 70 in the sequence listing.
3-732 (FL2), and SEQ ID NOs: 733-766.
It encodes a peptide consisting of the amino acid sequence of any one of (FL3).

The polynucleotide of the present invention also comprises
A peptide consisting of the amino acid sequence set forth in any one of SEQ ID NOS: 1 to 766 in the sequence listing, preferably SEQ ID NOS: 1 to 1.
It may be the one encoding the tumor antigen peptide consisting of the amino acid sequence described in any one of 7 and its complementary chain. Furthermore, the polynucleotide of the present invention comprises at least about 15 or more, preferably about 2 or more, corresponding to the region encoding the tumor antigen epitope of the peptide of the present invention.
It may be a polynucleotide having a base sequence of 1 to 30 or more and its complementary strand. The selection of this useful polynucleotide and the determination of its nucleotide sequence can be carried out by, for example, utilizing a known protein expression system, and recognizing the expressed peptide by CTL and / or confirming its CTL inducing ability.

Furthermore, a polynucleotide that hybridizes to the above-mentioned polynucleotide under stringent conditions is also included in the scope of the present invention. Taking a DNA molecule as a typical example of a polynucleotide molecule, a “DNA molecule that hybridizes to a DNA molecule under stringent conditions” refers to, for example, Molecular Cloning:
A Laboratory Manual (Sambr
ook et al., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1989) and the like. Here, “hybridize under stringent conditions” means, for example, 6 × SSC, 0.
42 ° C in a solution of 5% SDS and 50% formamide
It is shown that a positive hybridizing signal is still observed even under the condition of washing at 68 ° C. in a solution of 0.1 × SSC and 0.5% SDS after heating at.

The above-mentioned polynucleotide is HLA-A24.
HLA-A24-restricted antigen-specific CTL can be induced and / or recognized by the CTL when expressed in cells having Further, although the polynucleotide has a poly (A) structure at its 3 ′ end, the number of poly (A) does not affect the coding site of the amino acid acting as a tumor antigen, The number of poly (A) 's possessed by is not particularly limited.

The polynucleotides of the present invention all provide genetic information useful for the production of the peptides of the present invention, or can be used as reagents and standard products as nucleic acids.

(Recombinant Vector) A recombinant vector can be obtained by incorporating the above-mentioned polynucleotide into an appropriate vector DNA. The vector DNA used is appropriately selected depending on the type of host and the purpose of use. Vector D
The NA may be one obtained by extracting a naturally occurring one, or may be one in which a part of DNA other than the part necessary for growth is partially deleted. For example, vectors derived from chromosomes, episomes and viruses, such as bacterial plasmids, bacteriophages, transposons, yeast episomes, insertion elements, yeast chromosome elements, such as baculovirus, papovavirus, SV.
40, vectors derived from viruses such as vaccinia virus, adenovirus, fowlpox virus, pseudorabies virus and retrovirus, and vectors combining them, such as plasmids and vectors derived from genetic elements of bacteriophage, such as cosmid and phagemid. Etc. can be given. Moreover, an expression vector, a cloning vector, or the like can be used depending on the purpose.

The recombinant vector comprises, as constituent elements, a gene sequence of interest and a gene sequence carrying information on replication and control, such as a promoter, a ribosome binding site, a terminator, a signal sequence and an enhancer, which are known per se. It is produced by combining the methods. As a method for incorporating the polynucleotide of the present invention into the vector DNA, a method known per se can be applied.
For example, a method is used in which an appropriate restriction enzyme is selected and treated to cut the DNA at a specific site, which is then mixed with DNA similarly used as a vector and religated with ligase. Alternatively, the desired recombinant vector can also be obtained by ligating an appropriate linker to the polynucleotide of interest and inserting this into the multi-cloning site of the vector suitable for the purpose.

(Transformant) A vector DNA having the above-mentioned polynucleotide incorporated therein is introduced into a host known per se, such as Escherichia coli, yeast, Bacillus subtilis, insect cells, animal cells, etc., by a method known per se. A transformant is obtained. In the case of introducing a gene, a more preferable system is the method of integrating into the chromosome if the stability of the gene is taken into consideration. For convenience, an autonomous replication system utilizing an extranuclear gene can be used. Vector DNA
Is introduced into a host cell by, for example, Molecular
Cloning: A Laboratory Manu
al (Edited by Sambrook et al., Cold Spring)
It can be carried out by a standard method described in Harbor Laboratory Press, Cold Spring Harbor, New York, 1989) and the like. Specifically, calcium phosphate transfection, DEAE
-Dextran mediated transfection, microinjection, cationic lipid mediated transfection, electroporation, transduction, scrape loading, ballistic transduction.
n) and infection etc. can be illustrated.

(Production of peptide) If an expression vector is used as the vector DNA to be introduced into the above transformant,
A peptide according to the present invention can be provided. The transformant into which the expression vector DNA incorporating the above-mentioned polynucleotide has been introduced is cultured under optimal culture conditions known per se for each host. Culturing is carried out by using the action of the peptide of the present invention expressed by the transformant, particularly at least the action of inducing and / or activating CTL, or the amount of the peptide or peptide produced in the host or outside the host as an index. Alternatively, subculture or batch culture may be performed using the amount of transformant in the medium as an index.

The peptide of the present invention can be produced by a method known in ordinary peptide chemistry. For example, Peptide Synthesis (Maruzen), 1975, "Peptide S
synthesis, Interscience, New
York, 1996 ″ is exemplified, but, of course, known methods are widely available.

The peptide according to the present invention can be recovered by recognizing the peptide by CTL as an index, for example, the amount of IFN-γ produced from the CTL as an index, molecular sieve, ion column chromatography, affinity chromatography, etc. It is possible to purify and recover by a combination of the methods described above or by fractionation means based on the difference in solubility using ammonium sulfate, alcohol and the like. More preferably, a method of producing an antibody specific to the amino acid sequence of the peptide according to the present invention based on the information of the amino acid sequence, and using the obtained polyclonal antibody or monoclonal antibody to specifically adsorb and collect the antibody is used. .

(Antibody) The antibody according to the present invention is produced using the above peptide as an antigen. The antigen may be the peptide itself or a fragment thereof and is composed of at least 5 and more preferably at least 8-10 amino acids. In order to produce an antibody specific to the above peptide, it is preferable to use a region consisting of an amino acid sequence unique to the peptide. This amino acid sequence does not necessarily have to be homologous to the amino acid sequence of the peptide, and is preferably an externally exposed site on the three-dimensional structure of the peptide, even if the amino acid sequence of the exposed site is discontinuous on the primary structure. The amino acid sequence may be continuous for the exposed site. The antibody is not particularly limited as long as it immunologically binds or recognizes the peptide. The presence or absence of this binding or recognition is determined by a known antigen-antibody binding reaction.

In order to produce the antibody, a method known per se for producing an antibody can be used. For example, it can be obtained by administering the peptide according to the present invention alone or in combination with a carrier in the presence or absence of an adjuvant to an animal to induce immunity such as humoral response and / or cellular response. The carrier is not particularly limited as long as it does not have a harmful effect on the host, and examples thereof include cellulose, polymerized amino acids,
Albumin and the like are exemplified. As the animal to be immunized, mouse, rat, rabbit, goat, horse, etc. are preferably used.

The polyclonal antibody is obtained from the serum of the animal immunized as described above by a method known per se for antibody recovery. An immunoaffinity chromatography method is mentioned as a preferable means.

In order to produce a monoclonal antibody,
Antibody-producing cells (for example, spleen or lymph node-derived lymphocytes) are collected from the animal to which the above-mentioned immunization means has been applied, and permanently proliferating cells known per se (for example, P3-X63-Ag).
8 strains such as myeloma strain). For example, an antibody-producing cell and a permanently proliferating cell are fused by a method known per se to prepare a hybridoma, which is then cloned, and a hybridoma which produces an antibody specifically recognizing the peptide is selected, and the hybridoma of the hybridoma is selected. The antibody is recovered from the culture solution.

The thus obtained polyclonal antibody or monoclonal antibody capable of recognizing and binding to the peptide can be used as an antibody for purification of the peptide, a reagent, a labeling marker or the like.

(Screening) The above peptides, polynucleotides encoding them and their complementary chains, the above recombinant vectors, transformants into which the recombinant vectors are introduced, or antibodies that immunologically recognize these,
A single substance or a combination of a plurality of substances provides an effective means for identifying a substance capable of enhancing the recognition of the peptide by CTL. The identification method can be constructed using a drug screening system known per se. For example, as shown in the examples, the induction of CTL by the antigen-presenting cells pulsed with the tumor antigen peptide and / or the recognition by the CTL of the antigen-presenting cells is measured using the amount of IFN-γ produced from CTL as an index. A substance that enhances the recognition of the peptide according to the present invention by CTL can be selected by using an experimental system and adding a test substance thereto. This experimental system explains one of the identification methods, and the identification method according to the present invention is not limited to this.

The present invention is also directed to the compounds obtained by the above identification method. The compound is a peptide according to the present invention, for example, a peptide consisting of the amino acid sequence set forth in any one of SEQ ID NOS: 1 to 766 in the sequence listing, preferably the amino acid set forth in any one of SEQ ID NOS: 1 to 17 in the sequence listing. It may be a peptide consisting of a sequence and / or a compound that interacts with HLA-A24 and enhances the recognition of the peptide by HLA-A24-restricted CTL. Further, a compound or the like that interacts with the polynucleotide of the present invention to enhance its expression is also included in the scope of the present invention. The compounds thus selected can be prepared as pharmaceutical compositions by selecting in consideration of the balance between biological utility and toxicity.

(Pharmaceutical Composition) The peptide according to the present invention is
As a tumor antigen, it can be used to induce and / or activate HLA-A24-restricted antigen-specific CTL. That is, a method for inducing CTL characterized by using the above peptide and CT containing the above peptide
L inducers are also included within the scope of the invention.

Further, the peptide according to the present invention, the polynucleotide encoding the peptide and its complementary chain, the recombinant vector according to the present invention, the cell into which the recombinant vector is introduced, the antibody that immunologically recognizes the peptide Interacting with the peptide and / or HLA-A24
A compound that enhances the recognition of the peptide by the above, or a compound that interacts with the polynucleotide and enhances the expression thereof, alone or in combination, is used to provide a pharmaceutical composition containing at least one of these compounds. Can be provided. H, one of the polymorphisms in the HLA-A subregion
The LA-A24 allele is about 60% of the Japanese population (often 95% of which have A24 genotype).
02), 20% of Caucasians, 1 of Africans
Since it is found in 2%, the pharmaceutical composition according to the present invention is
The effect can be expected in many patients.

Furthermore, peptides according to the invention, such as M
The mRNA of RP3 is a lung cancer cell line, an ovarian cancer cell line, and a renal cancer cell line (lung cancer cell line: 11-18, QG56, S
Q-1, RERF-LCM, SLC1-Sq, LC65
A, RERF-LCA1, LK79, PC-9, and 1-87; ovarian cancer cell lines: KOC-3S, KOC-5.
C, KOC-7C, TYK-nu, RMUG-S, RM
G-1, TOC-2, MCAS, RTSG, and RK
N: Renal cancer cell line: PC93, RC30-14, PC3,
VMRC-RCW, TUHR-4TKB, TUHR-1
0TKB, RCC-10RGB, and LNCap) and the like. Expression of MRP3 was also observed in various tissues derived from patients with lung cancer, renal cancer, colon cancer, gastric cancer, ovarian cancer, esophageal cancer, and oral cancer. Therefore, the above-mentioned pharmaceutical composition is useful in the treatment of cancer such as lung cancer, renal cancer, colon cancer, gastric cancer, ovarian cancer, esophageal cancer and oral cancer.

Specifically, for example, a medicine comprising the peptide of the present invention and a pharmaceutical composition containing the peptide of the present invention can be used as a so-called cancer vaccine.
At this time, in order to stimulate cell-mediated immunity, the peptide according to the present invention is present in the presence or absence of an appropriate adjuvant,
Used alone or bound to a carrier. The carrier is
There is no particular limitation as long as it does not have a harmful effect on the human body, and examples thereof include cellulose, polymerized amino acids, and albumin. The dosage form can be appropriately selected by applying a means for formulating a peptide known per se. Although the dose varies depending on the degree of recognition of the peptide by CTL, it is generally 0.01 mg to 10 mg as the active substance.
0 mg / day / adult human, preferably 0.1 mg to 10 m
g / day / adult human. This is administered once every several days to several months.

Alternatively, a mononuclear cell fraction is collected from the peripheral blood of a patient and cultured with the peptide of the present invention, and the mononuclear cell fraction in which CTL is induced and / or activated is introduced into the blood of the patient. An effective cancer vaccine effect can also be obtained by returning it. Culture conditions such as the concentration of mononuclear cells at the time of culturing and the concentration of the peptide according to the present invention can be determined by a simple experiment. In addition, a substance having a lymphocyte proliferation ability such as interleukin-2 may be added during the culture.

When the peptide according to the present invention is used as a cancer vaccine, only one peptide is effective as a cancer vaccine, but it is also possible to use a plurality of kinds of the above peptides in combination. Since CTLs of cancer patients are a population of cells that recognize multiple tumor antigens, it is sometimes more effective to use a combination of multiple peptides as a cancer vaccine rather than a single peptide as a cancer vaccine. is there. Furthermore, it has been reported that the expression of the peptide of the present invention, such as MRP3, in tumor cell lines is increased by commonly known anticancer agents such as doxorubicin and cisplatin (E.
ur. J. Cancer, 32: 94-657, 199.
6) (Multidrug Resistance i
nCancer Cells: 98-107, New
York: John Wiley & Sons, 199
6) [J. Natl. Cancer Inst. (Be
thesda), 92: 11295-1302, 200.
[0], when the peptide, the pharmaceutical composition or the cancer vaccine according to the present invention is used together with these anticancer agents, it may be easily conceivable that a high preventive and / or therapeutic effect on cancer may be obtained.

The polynucleotide encoding the peptide according to the present invention and its complementary chain are useful for gene therapy of cancer such as lung cancer, renal cancer, colon cancer, gastric cancer, ovarian cancer, esophageal cancer, and oral cancer. Is. There is a method of carrying these polynucleotides on a vector and directly introducing them into the body, or a method of collecting cells from human and then introducing them outside the body, and either method can be used. As the vector, retrovirus, adenovirus, vaccinia virus, etc. are known, but the retrovirus system is recommended. Of course, these viruses are replication defective. The dose is CT
Although it varies depending on the degree of recognition of the peptide encoded by the polynucleotide by L, the content of DNA encoding the tumor antigen peptide of the present invention is generally 0.1 μm.
g to 100 mg / day / adult human, preferably 1 μg to 5
0 mg / day / adult human. This is administered once every several days to several months.

(Measurement Method and Reagent for Diagnosis) The peptide of the present invention, the polynucleotide encoding the peptide and its complementary chain, and the antibody which immunologically recognizes the peptide are themselves singly, It can be used as a diagnostic marker or reagent. The present invention also provides a reagent kit comprising one or more containers filled with one or more of these. In addition,
For formulation, a formulation means suitable for each peptide, polynucleotide, antibody or the like known per se may be introduced.

The method for diagnosing a disease related to the expression or activity of the peptide according to the present invention utilizes the interaction or reactivity with the polynucleotide encoding the peptide to determine the abundance of the corresponding nucleic acid. Determining and / or determining the biodistribution of the peptide in the individual, and / or determining the presence of the peptide, its abundance in a sample from the individual. That is, the peptides according to the present invention or the nucleic acids encoding them are qualitatively or quantitatively measured as diagnostic markers. A method well known to those skilled in the art can be used for a quantitative or qualitative measurement method of the peptide of interest or a nucleic acid encoding them in a sample. Such assays include radioimmunoassays, competitive-binding assays, Western blot analysis and enzyme-linked immunosorbent assay (ELIS).
A) etc. In addition, the nucleic acid may be, for example, amplified, PCR, R
RN using T-PCR, RNase protection, Northern blotting and other hybridization methods
Detection and quantification at A level is possible.

As a sample to be measured, cells derived from an individual,
For example, blood, urine, saliva, spinal fluid, tissue biopsy or autopsy material and the like can be exemplified. The nucleic acid to be measured can be obtained from each of the above samples by a nucleic acid preparation method known per se. Nucleic acids may use genomic DNA directly for detection, or may be enzymatically amplified by using PCR or other amplification methods prior to analysis. RNA or cDNA may be used as well. In addition, deletions and insertions can be detected by the size change of the amplification product in comparison with the normal genotype. Point mutations can be identified by hybridizing amplified DNA to labeled DNA encoding the above peptides.

By detecting the mutation, decrease or increase in the peptide of the present invention and the DNA encoding the peptide by the above-mentioned measurement, diseases associated with the peptide, such as lung cancer, renal cancer, colon cancer, gastric cancer, ovary, etc. It becomes possible to diagnose cancer, esophageal cancer, oral cancer and the like.

[0063]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.

Example 1 (Establishment of HLA-A24-restricted CTL) H
The LA-A24-restricted tumor-specific cytotoxic T lymphocyte line (CTL) was used in lung cancer patients (HLA-A2402 / A0).
206) tumor-infiltrating lymphocytes (TIL) according to the method described in the literature (Int. J. Cancer).
r, 81: 459-466, 1999, J. Immun
ol. , 163: 4997-5004, 1999). First, TIL obtained from a lung cancer patient was added with 100 U / ml of recombinant human interleukin-2 (IL-2) to give 5
Long-term culture was performed for 0 days or more. A part of these IL-2 activated TILs was collected every 7 days of culture, cultured with various tumor cells or normal cells, and its CTL activity was assayed by measuring IFN-γ production (J. Immunol., 16
3: 4997-5004, 1999). IFN-γ was measured by enzyme-linked immunosorbent assay (ELISA).

The obtained CTL (hereinafter referred to as GK-CTL) is HLA-A2402 ⁺ 11-, as shown in FIG.
It recognized 18 lung cancer cell lines, Sq-1 lung cancer cells, and PC9 lung cancer cells, and produced IFN-γ. But HL
A-A24 ^- Tumor cells, COS-7 cells, and VA-
13 cells were not recognized. From this, GK-CT
It was confirmed that L is HLA-A24 restricted CTL.

The genotype of the HLA class I allele of the above tumor cells has been reported previously (Canc. Immuno).
l. Immunother. , 48: 147-152,
1999). The HLA class I serotype of the patient was determined by a conventional serological method using peripheral blood mononuclear cells (PBMC). Furthermore, HLA-A
The 2 / A24 subtype was determined by a sequence-specific oligonucleotide probe method and a DNA sequencing method (dideoxynucleotide sequencing method).

[0066]

Example 2 (Isolation / Identification of cDNA Clone Encoding Tumor Antigen) The gene encoding the tumor antigen of human lung cancer cell line 11-18 recognized by GK-CTL obtained in Example 1 is known. Method (J. Immunol., 16
3: 4997-5004, 1999).
Identified. First, poly (A) ⁺ R of 11-18 cells
NA was converted into cDNA and ligated with SalI adaptor, and expression vector pCMV-SPORT-2
(Manufactured by Invitrogen). Also, HL
A-A2402 cDNA was obtained by reverse transcription-polymerase chain reaction (PCR), and eukaryotic expression vector pC
It was cloned into R3 (Invitrogen).

The above cDNA obtained from 11-18 cells
100 clones of each clone were pooled, and 200 ng of the pooled cDNA and HLA-A240 were pooled for each well.
200 ng of 2 cDNA and 100 μl of lipo
photoamine (manufactured by Invitrogen) /
Opti-MEM (manufactured by Invitrogen) 1: 2
It mixed in the 00 liquid mixture for 30 minutes. 50 μl of this mixture
Was added to COS-7 cells (1 × 10 ⁵ ) and incubated for 6 hours for co-transfection. Then 10% FC
RPMI-1640 medium containing S was added and cultured for 2 days, and GK-CTL (2 × 10 ⁴ ) was added to each well. After further incubation for 18 hours, 100 μl of the supernatant was taken and the produced IFN-γ was subjected to ELISA.
A pool of cDNA libraries was screened as determined by A. At this time, IFN-γ production by GK-CTL was examined using COS-7 cells into which no gene was introduced as a negative control, and the value of IFN-γ produced was subtracted from each measurement value as the background. .

As a result, reproducibility was confirmed for the pool of the 11-18 cell cDNA library which promoted the production of IFN-γ from CTL, and then clones were individually taken out from the cDNA pool in which the reproducibility was confirmed.
Screening was performed in the same manner as above to select clones derived from an independent pool recognized by CTL. Furthermore, the dose dependency of the obtained clone was confirmed by the same method as above,
Finally 8 types of clones, namely clone 5, clone 114, clone 50, clone 83, clone 1
11, clone 96, clone 122, clone 19-
5-114 was obtained. These eight types of cDNA clones were respectively cossed with HLA-A2402cDNA.
-7 cells co-transfected with GK in a dose-dependent manner
-It was recognized by CTL and promoted IFN-γ production.
However, these cDNA clones were cloned into HLA-A260
When co-transfected with 2cDNA, GK-C
No enhancement of IFN-γ production from TL was observed.
Clone 5, clone 114, clone 50, clone 83, clone 111, clone 96, and clone 122 are shown in FIGS. 2 to 8, respectively. From this, it was confirmed that the obtained cDNA clone encodes a tumor antigen that can be recognized by GK-CTL in a HLA-A24-restricted manner. On the other hand, the expression vector pCM
In COS-7 cells in which V-SPORT-2 alone was co-transfected with each type of HLA, IF from GK-CTL was detected.
N-γ production was not promoted (not shown).

The nucleotide sequence of the obtained cDNA clone was determined by the DNA sequencing kit (Perkin-
ABI PRISM ^™ 37
7DNA Sequencer (Perkin-Elm
(manufactured by er, Inc.) was used for the dideoxynucleotide sequencing method. Furthermore, the amino acid sequences encoded by the respective genes were deduced for the open reading frames of frame 1, frame 2 and frame 3 from the obtained base sequences (SEQ ID NOs: 767 to 774 in the sequence listing). Also,
Clone 19-5-114 was found to be an alternative splicing variant of clone 114 as a result of sequencing.

[0070]

Example 3 (Establishment of GK-CTL Subline) GK-
CTL sublines are from GK-CTL parental strains in limiting dilution cultures (0.3, 0.5, 1, 2 and 4 cells / well).
Established by [J. Immunol. , 163,4
997-5004, 1999]. These sub-lines consist of 100 ng / well of each of the above genes and HLA-A2.
100 ng / well of 402 cDNA was cultured with COS-7 cells or tumor cells into which cogene was introduced at a cell ratio of 1: 1 and the amount of IFN-γ produced was used as an index for selection. Of these sublines, four types of CTL sublines are clone 5 (MRP3), three types of CTL sublines are clone 50, five types of CTL sublines are clone 83, and three types of CTL sublines are clone 96.
(HBP) 3 types of CTL sublines are clone 11
1, 1 type of CTL subline is clone 114, and 2 types of CTL subline is clone 122 (ZF
It showed reactivity to COS-7 cells expressing N) (Table 2). That is, it was revealed that the tumor antigen peptides recognized differ depending on the CTL subline. From this, it was suggested that GK-CTL, that is, CTL of cancer patients, is a population of cells that recognize multiple tumor antigens.

[0071]

[Table 2]

[0072]

Example 4 (Preparation of tumor antigen peptide and its CT
L-inducing activity) In order to obtain a tumor antigen peptide from the 8 types of genes encoding the tumor antigens isolated and identified in Example 2, first, based on a motif (regular sequence) capable of binding to HLA-A24, it was reported previously. [Kawano K. et a
l. , Cancer Res. 60: 3550-355
8 (2000)] [Ibe M. et al. et al. , Imm
ungenetics 44: 233-241 (19).
96)], the amino acid sequences encoded by the genes 1 to 8 and the amino acid sequences of the gene products of MRP3, HBP, and ZFN having high homology with the genes are different from each other by 9 mer or 10 mer.
A mer peptide was designed, and a total of 72 kinds of peptides (purity of 70% or more) were synthesized by a method known per se. Three
One is clone 5 (Table 3), 10 is clone 11
4 (Table 4), one is clone 19-5-114 (Table 4
114-3-54), 6 types of clone 50
(Table 5), 11 kinds of clone 83 (Table 6), 2 kinds of clone 111 (Table 7), 7 kinds of clone 96 (Table 8), 3 kinds of clone 122 (Table 9), 1 kind of ZF
It is a peptide designed from the amino acid sequence encoded by the N gene (peptide 122-20 in Table 9).

[0073]

[Table 3]

[0074]

[Table 4]

[0075]

[Table 5]

[0076]

[Table 6]

[0077]

[Table 7]

[0078]

[Table 8]

[0079]

[Table 9]

Each peptide synthesized above (final concentration 10 μm
M) is a C1R cell into which HLA-A2402 is introduced (hereinafter referred to as C1R / A2402 cell), and 5% C
HLA in which each peptide was expressed on the cell surface by incubation in O ₂ -95% Air at 37 ° C. for 2 hours
Bound to A2402. C1R / A2402 cells pulsed with each peptide in this manner were used as target cells (T). In addition, GK-CTL was used as effector cells (E). 1 × 10 ⁴ target cells and 2 × 10 ⁴ effector cells were mixed (E / T ratio = 2), 1
I incubated for 8 hours. 100 μl of the supernatant after the incubation was recovered and IFN was analyzed by ELISA.
-Γ was measured. C1R / not pulsed with peptide
IFN-γ production of CTL against A2402 cells was used as a background, and subtracted from each measurement value. as a result,
Each of the 17 kinds of peptides shown in Table 1 above is GK-C.
It was recognized by TL and promoted IFN-γ production of GK-CTL. The results are shown in FIGS. 9 to 15.

Further, among the 17 kinds of peptides recognized by GK-CTL, 4 kinds derived from clone 5 (peptides 5-503, 5-692, 5-765 and 5-1293) and clone 114 were derived. 1 type (peptide 114-1-275), clone 19-5-11
Dose dependence was examined for one type from 4 (peptide 114-3-54) and two types from clone 50 (peptides 50-1-767 and 50-2-383). Recognized by GK-CTL,
IFN-γ production of GK-CTL was promoted (FIGS. 16 to 2).
3).

[0082]

[Example 5] (CTL induction from peripheral blood mononuclear cells of cancer patients by peptide) Of the tumor antigen peptides obtained in Example 4, two types derived from clone 50 (peptide 50-1-7)
67 and 50-2-383), 2 from clone 83.
Type (Peptides 83-3-297 and 83-3-30
1), one kind derived from clone 96 (peptide 96-3-
380), one kind derived from clone 111 (peptide 11
1-3-815), one kind derived from clone 114 (peptide 114-1-275), and clone 19-5.
The in vitro CTL inducing ability from human peripheral blood mononuclear cells (PBMC) was examined for one type from 114 (peptide 114-3-54) using IFN-γ production as an index. PBMCs were prepared from the peripheral blood of 6 HLA-A24-positive lung cancer patients and 6 healthy volunteers by a conventional method. First, 1 × 10 ⁵ PBMCs were added to each well of a 96-well U-bottom microculture plate (manufactured by Nunc) and incubated with 10 μg / ml of each peptide in 200 μl of culture medium.
The medium is 45% RPMI-1640, 45% AIM-V
(Invitrogen), 10% fetal calf serum (FC
S), 100 U / ml human interleukin-2,
And a 0.1 μM MEM non-essential amino acid solution (Invitrogen). Every 3rd day of culture, half the amount of the medium was removed, and the medium was replaced with a medium having the above composition containing each corresponding peptide. In this way, the peptide stimulation by medium exchange was performed 5 times, and the cells were collected and washed the day after the final stimulation and reacted with the target cells. The amount of IFN-γ produced in the supernatant was the same as in Example 4. Measured. As target cells, 11-18 lung cancer cells (H
LA-A24 ⁺ ) or C1R / A2402 cells pulsed with the corresponding peptides were used. At this time, QG5
IF of CTL for 6 cells (HLA-A24 ⁻ ) or C1R / A2402 cells pulsed with HIV peptide
Using N-γ production as the background, 11-18 lung cancer cells or C1R / A2402 cells pulsed with each peptide were subtracted from the measurements obtained when used as target cells. In addition, the Epstein Barr virus (EB
A peptide matching the HLA-A24 binding motif from V) was used as a positive control.

The results are shown in FIGS. 24 to 26. FIG. 24 shows the results using PBMC derived from a lung cancer patient who was peptide-stimulated as effector cells and C1R / A2402 cells pulsed with the corresponding peptide as target cells. FIG. 25 shows the results using peptide-stimulated lung cancer patient-derived PBMCs as effector cells and 11-18 lung cancer cells as target cells. FIG. 26
Shows the results using PBMC derived from a healthy person who was peptide-stimulated as effector cells and C1R / A2402 cells pulsed with the corresponding peptide as target cells. In the figure, each bar corresponds to the results for PBMC obtained from 6 lung cancer patients or healthy subjects.

As shown in FIG. 24 and FIG. 25, PBMCs derived from lung cancer patients, which were respectively incubated with the above 8 kinds of peptides, were the same as the peptides used for stimulation, and were pulsed with C1R / A2402 cells, or 11-. It recognized 18 lung cancer cells and promoted the production of IFN-γ. That is, the above-mentioned 8 kinds of peptides recognize these peptides from PBMCs of lung cancer patients and recognize IFN-
HLA-A24-restricted CTL that promote γ production could be induced in vitro. On the other hand, as shown in FIG. 26, in PBMC obtained from a healthy person, peptide 114-1-
With the exception of 275, the reaction with C1R / A2402 cells pulsed with the same peptide as each peptide used for stimulation did not show or showed a low level of IFN-γ production. It is considered that the degree of CTL induction by each peptide varies among cancer patients because it is a population of cells that recognize multiple antigens when CTL is already a precursor.

Further, the above-mentioned PBMC derived from a lung cancer patient stimulated five times with a peptide was further treated in the absence of the peptide and with IL.
After culturing for 1 month in the presence of C-2 (100 units / ml), the cytotoxicity of the obtained cells against 11-18 lung cancer cells was measured at a standard E / T ratio of 2.5: 1 to 20: 1. The results were expressed in% specific lysis as measured by the 6 hour ⁵¹ Cr release test (FIG. 27). At the same time HLA-
Cytotoxicity was measured against A24 ^- tumor cells, QG56 lung cancer cells.

As a result, the PBMC derived from the above-described peptide-stimulated lung cancer patient showed HLA-A depending on the E / T ratio.
It recognized 11-18 lung cancer cells, which are 24 ⁺ tumor cells, and showed cytotoxicity. However, it did not show cytotoxicity against HLA-A24 ^- tumor cells, QG56 cells. A representative example is shown in FIG. That is, the above-mentioned 8 kinds of peptides were found to be
4 CTL that recognizes tumor cells and shows cytotoxicity
Was induced.

[0087]

Example 6 Of the tumor antigen peptides obtained in Example 4,
Four kinds of peptides derived from MRP3 (MRP3-503,
MRP3-692, MRP3-765 and MRP3-
1293), human peripheral blood mononuclear cells (PBMC)
The in vitro CTL inducing ability of Escherichia coli was examined using IFN-γ production as an index. All PBMCs are HLA-
The preparation was carried out in the usual manner from the peripheral blood of 3 A24-positive lung cancer patients, 4 renal cancer patients, 2 colon cancer patients, and 3 healthy subjects. The obtained PBMCs and 10 μM each of the above peptides were cultured in the same manner as in Example 5, and peptide stimulation was performed 4 times. The day after the final stimulation, cells were collected, washed, reacted with target cells, and produced in the supernatant.
The N-γ amount was measured in the same manner as in Example 4. As the target cells, Sq-1 lung cancer cells (HLA-A24 ⁺ ) or C1R / A2402 cells pulsed with the corresponding peptides were used. At this time, QG56 cells (HLA-A24 ^-)
Or C1R / A2402 not pulsed with peptide
With the background being CTL IFN-γ production against cells, Sq-1 lung cancer cells or C1R / A2402 cells pulsed with each peptide were subtracted from the measurement values obtained when used as target cells. Also, Epstein
A peptide compatible with the HLA-A24 binding motif derived from Barr virus (EBV) was used as a positive control.
HIV derived peptides were used as a negative control. The results are shown in FIGS. 28 and 29.

FIG. 28 shows the results of PBMCs derived from lung cancer patients as a representative example. 28A
As is clear from the above, the PBMCs respectively incubated with the four kinds of peptides derived from MRP3 showed Sq
-1 lung cancer cells (HLA-A24 ⁺ ) or C1R / A24 pulsed with the same peptide as each peptide used for stimulation
02 cells were recognized and IFN-γ production was promoted. That is, the above four kinds of peptides are HLA-A24-restricted CT that recognizes these peptides and promotes IFN-γ production.
L could be derived in vitro from PBMCs of lung cancer patients. Furthermore, as a result of examining the specificity of peptide recognition for the induced CTLs, as shown in FIG. 28B, the CTLs induced by each peptide were C1R / A2402 pulsed with each peptide used for stimulation. Although the cells were recognized and IFN-γ production was promoted, the cells pulsed with other peptides showed low recognition and IFN-γ production. That is, the CTL induced by each peptide is
It was found to specifically recognize the peptide used for the induction.

Further, as shown in FIG. 29, PBMC obtained from 3 lung cancer patients, 4 renal cancer patients and 2 colon cancer patients stimulated by each of the above 4 kinds of peptides were used for stimulation. C1R pulsed with the same peptide as each peptide
/ A2402 cells and / or Sq-1 lung cancer cells (H
LA-A24 ⁺ ) was recognized and IFN-γ production was promoted (FIGS. 29A and 29B). On the other hand, PBM obtained from healthy people
In C, even when stimulated with these peptides, the amount of IFN-γ produced for the target cells was low. That is, the above four peptides recognize HLA-A24-restricted CTL that recognizes these peptides and promotes IFN-γ production.
For PBMCs of lung cancer patients, renal cancer patients, and colon cancer patients
Was derived in vitro.

Further, the above-mentioned PBMC derived from a cancer patient, which was stimulated four times with the peptide, was further cultured after irradiation with autologous PBMC pulsed with the corresponding peptide as an antigen-presenting cell. On day 3 and day 7 of the culture, stimulation with peptide in the absence of antigen presenting cells
Cultured with L-2 only. The cells were collected on day 28 to 42 of culture and used as effector cells.
Cells against target cells using Sq-1 lung cancer cells or 11-8 lung cancer cells that are LA-A24 ⁺ tumor cells or HLA-A24 ⁺ EBV-transformed B cells pulsed with the same peptide used for stimulation Damaging
The measurement was performed in the same manner as in Example 5, and the obtained results were expressed by% specific lysis (FIG. 30). At the same time, the cytotoxicity against HLA-A24 ^- tumor cells, QG56 lung cancer cells, was measured.

As a result, cancer patients stimulated with the above peptides
PBMCs derived from humans depend on the E / T ratio and
It recognized the vesicles and showed cytotoxicity. However, HLA-A
24 ⁻Cytotoxicity against tumor cells, QG56 cells
It showed no sex. Typical examples are shown in A and B of FIG.
Show. That is, the four types of peptides derived from the above MRP3
PBMC of lung cancer patient, renal cancer patient, or colon cancer patient
From HLA-A24-restricted recognition of tumor cells
Induced CTLs showing damaging effects. Also, from B of FIG.
As can be seen, the CTL induced by MRP3-503
Recognizes cells pulsed with MRP3-503, but MR
The cells pulsed with P3-765 were not recognized, and conversely MRP
The CTL induced by 3-765 was found to induce MRP3-765.
Recognize loose cells but pulse MRP3-503
Since it does not recognize the cells that
The derived CTL was characterized by the peptide specificity used for the induction.
It was confirmed to be recognized differently.

Furthermore, it was confirmed that the recognition of tumor cells by the above-mentioned CTL was associated with the expression of MRP3 in the tumor cells. That is, the CTLs are HLA-A24 ⁺ and Sq-1 lung cancer cells expressing MRP3 and TU.
Recognized HR-10 TKB renal cancer cells and promoted IFN-γ production, but HLA-A24 ⁺ and low MRP3 expression Caki-1 renal cancer cells and HLA-A24 ⁻ and low MRP3 expression KUR-11 renal carcinoma cells, and HLA-A24 ^- an a by expressing MRP3 QG
The level of recognition of 56 lung cancer cells and the amount of IFN-γ production were low. The results are shown in FIG. 31A by taking the CTL induced from the lung cancer patient-derived PBMC by the MRP3-derived peptide as an example. Furthermore, when Maki3-renal cancer cells, which originally have low expression of MRP3, were pulsed with MRP3-692, as shown in B of FIG. 31, MRP3-6 was detected.
It was found to be recognized by CTL induced by 92 stimuli. On the other hand, Caki- pulsed with HIV peptide
1 Renal cancer cells were induced by MRP3-692 C
Not recognized by TL.

Moreover, the MRP was evaluated using various tumor cell lines.
3 When the expression of mRNA was examined by Northern blotting, the expression of MRP3 was confirmed in all 10 types of lung cancer cell line, ovarian cancer cell line, and renal cancer cell line examined, except 2 types of renal cancer cell lines. (Lung cancer cell line:
11-18, QG56, SQ-1, RERF-LCM,
SLC1-Sq, LC65A, RERF-LCA1, L
K79, PC-9, and 1-87; ovarian cancer cell line: K
OC-3S, KOC-5C, KOC-7C, TYK-n
u, RMUG-S, RMG-1, TOC-2, MCA
S, RTSG, and RKN; renal cancer cell line: PC93,
RC30-14, PC3, VMRC-RCW, TUHR
-4TKB, TUHR-10TKB, RCC-10RG
B, and LNCap). On the other hand, in COS-7 cells, VA13 cells, and 293T cells, which are non-neoplastic cell lines, and SS-EBB cells, which are EBV-transformed cells,
Expression of MRP3 was low. Expression of MRP3 was also observed in various tissues derived from patients with lung cancer, renal cancer, colon cancer, gastric cancer, ovarian cancer, esophageal cancer, and oral cancer. From this, the above-mentioned MRP3-derived peptide is HLA-A24-restricted not only to the 11-18 lung cancer cells and Sq-1 lung cancer cells used in the above study but also to various tumor cells expressing MRP3. CTL showing cytotoxicity
It is considered possible to induce. That is, the peptide derived from MRP3 is useful for the prevention and / or treatment of various cancers such as lung cancer, renal cancer, colon cancer, gastric cancer, ovarian cancer, esophageal cancer, and oral cancer.

[0094]

INDUSTRIAL APPLICABILITY According to the present invention, HLA-A24-restricted cytotoxic T cells can be induced and / or activated. It will be possible. The HLA-A24 allele is found in about 60% of the Japanese population (often 95% of which have A2402 genotype), 20% of Caucasians, and 12% of Africans. Therefore, the present invention can be expected to make a great contribution in the treatment of cancer. Further, the present invention greatly contributes to basic research of molecules related to recognition by T cells such as epithelial cancer and adenocarcinoma.

[0095]

[Sequence Listing Free Text] Sequence Listing SEQ ID NO: 1: Designed peptide that acts as a tumor antigen. SEQ ID NO: 2 in Sequence Listing: designed peptide that acts as a tumor antigen. SEQ ID NO: 3 in Sequence Listing: designed peptide that acts as a tumor antigen. SEQ ID NO: 4 in Sequence Listing: designed peptide that acts as a tumor antigen. Sequence number 5 of a sequence table: The designed peptide which acts as a tumor antigen. SEQ ID NO: 6 in Sequence Listing: designed peptide that acts as a tumor antigen. Sequence number 7 of a sequence table: The designed peptide which acts as a tumor antigen. Sequence number 8 of a sequence table: The designed peptide which acts as a tumor antigen. SEQ ID NO: 9 of Sequence Listing: designed peptide that acts as a tumor antigen. Sequence number 10 of a sequence table: The designed peptide which acts as a tumor antigen. Sequence number 11 of a sequence table: The designed peptide which acts as a tumor antigen. Sequence number 12 of a sequence table: The designed peptide which acts as a tumor antigen. Sequence number 13 of a sequence table: The designed peptide which acts as a tumor antigen. Sequence number 14 of a sequence table: The designed peptide which acts as a tumor antigen. Sequence number 15 of a sequence table: The designed peptide which acts as a tumor antigen. Sequence number 16 of a sequence table: The designed peptide which acts as a tumor antigen. Sequence number 17 of a sequence table: The designed peptide which acts as a tumor antigen.

[0096]

[Sequence list]                                SEQUENCE LISTING    <110> ITOH, Kyogo    <120> Tumor Antigen    <130> NP01-1093    <140> <141>    <150> JP P2000-304155 <151> 2000-10-03    <150> JP P2001-121452 <151> 2001-04-19    <160> 774    <170> PatentIn Ver. 2.1    <210> 1 <211> 9 <212> PRT <213> Artificial Sequence    <220> <223> Description of Artificial Sequence: Designed       peptide acting as a tumor antigen    <400> 1 Leu Tyr Ala Trp Glu Pro Ser Phe Leu   1 5       <210> 2 <211> 9 <212> PRT <213> Artificial Sequence    <220> <223> Description of Artificial Sequence: Designed       peptide acting as a tumor antigen    <400> 2 Ala Tyr Val Pro Gln Gln Ala Trp Ile   1 5       <210> 3 <211> 9 <212> PRT <213> Artificial Sequence    <220> <223> Description of Artificial Sequence: Designed       peptide acting as a tumor antigen    <400> 3 Val Tyr Ser Asp Ala Asp Ile Phe Leu   1 5       <210> 4 <211> 10 <212> PRT <213> Artificial Sequence    <220> <223> Description of Artificial Sequence: Designed       peptide acting as a tumor antigen    <400> 4 Asn Tyr Ser Val Arg Tyr Arg Pro Gly Leu   1 5 10       <210> 5 <211> 10 <212> PRT <213> Artificial Sequence    <220> <223> Description of Artificial Sequence: Designed       peptide acting as a tumor antigen    <400> 5 Ile Tyr Gly Gly Phe Trp Phe Phe Pro Ile   1 5 10       <210> 6 <211> 9 <212> PRT <213> Artificial Sequence    <220> <223> Description of Artificial Sequence: Designed       peptide acting as a tumor antigen    <400> 6 Ile Phe Gln Thr Asn Met Asp Ser Leu   1 5       <210> 7 <211> 10 <212> PRT <213> Artificial Sequence    <220> <223> Description of Artificial Sequence: Designed       peptide acting as a tumor antigen    <400> 7 Val Phe Leu Pro Cys Asp Ser Trp Asn Leu   1 5 10       <210> 8 <211> 9 <212> PRT <213> Artificial Sequence    <220> <223> Description of Artificial Sequence: Designed       peptide acting as a tumor antigen    <400> 8 Met Phe Lys Glu Pro Val Glu Val Leu   1 5       <210> 9 <211> 10 <212> PRT <213> Artificial Sequence    <220> <223> Description of Artificial Sequence: Designed       peptide acting as a tumor antigen    <400> 9 Leu Tyr Thr Phe Gly Val Leu Leu Asn Leu   1 5 10       <210> 10 <211> 10 <212> PRT <213> Artificial Sequence    <220> <223> Description of Artificial Sequence: Designed       peptide acting as a tumor antigen    <400> 10 Phe Phe Leu Ala Thr Leu Leu Ile Gly Leu   1 5 10       <210> 11 <211> 10 <212> PRT <213> Artificial Sequence    <220> <223> Description of Artificial Sequence: Designed       peptide acting as a tumor antigen    <400> 11 Ser Phe Lys His Ser Phe Ala Tyr Thr Leu   1 5 10       <210> 12 <211> 10 <212> PRT <213> Artificial Sequence    <220> <223> Description of Artificial Sequence: Designed       peptide acting as a tumor antigen    <400> 12 Ser Phe Ala Tyr Thr Leu Asn Phe Ile Leu   1 5 10       <210> 13 <211> 9 <212> PRT <213> Artificial Sequence    <220> <223> Description of Artificial Sequence: Designed       peptide acting as a tumor antigen    <400> 13 Lys Tyr Cys Val Leu Val Trp Ala Ile   1 5       <210> 14 <211> 10 <212> PRT <213> Artificial Sequence    <220> <223> Description of Artificial Sequence: Designed       peptide acting as a tumor antigen    <400> 14 Lys Tyr Leu Lys Leu Ser Ser Ser Glu Leu   1 5 10       <210> 15 <211> 10 <212> PRT <213> Artificial Sequence    <220> <223> Description of Artificial Sequence: Designed       peptide acting as a tumor antigen    <400> 15 Ile Phe Ser Tyr Cys Leu Ser Gly Gly Leu   1 5 10       <210> 16 <211> 10 <212> PRT <213> Artificial Sequence    <220> <223> Description of Artificial Sequence: Designed       peptide acting as a tumor antigen    <400> 16 Phe Tyr Gly Asn Pro Arg Thr Asn Gly Met   1 5 10       <210> 17 <211> 10 <212> PRT <213> Artificial Sequence    <220> <223> Description of Artificial Sequence: Designed       peptide acting as a tumor antigen    <400> 17 Asp Tyr Lys Ala Glu Ala Ala Ala Lys Ile   1 5 10          <210> 18 <211> 1541 <212> PRT <213> Homo sapiens    <400> 18 Val Arg Pro Arg Ser Pro Ser Leu Gln Pro Arg Pro Gly Pro Met Asp   1 5 10 15 Ala Leu Cys Gly Ser Gly Glu Leu Gly Ser Lys Phe Trp Asp Ser Asn              20 25 30 Leu Ser Val His Thr Glu Asn Pro Asp Leu Thr Pro Cys Phe Gln Asn          35 40 45 Ser Leu Leu Ala Trp Val Pro Arg Ile Tyr Leu Trp Val Ala Leu Pro      50 55 60 Cys Tyr Leu Leu Tyr Leu Arg His His Cys Arg Gly Tyr Ile Ile Leu  65 70 75 80 Ser His Leu Ser Lys Leu Lys Met Val Leu Gly Val Leu Leu Trp Cys                  85 90 95 Val Ser Trp Ala Asp Leu Phe Tyr Ser Phe His Gly Leu Val His Gly             100 105 110 Arg Ala Pro Ala Pro Val Phe Phe Val Thr Pro Leu Val Val Gly Val         115 120 125 Thr Met Leu Leu Ala Thr Leu Leu Ile Gln Tyr Glu Arg Leu Gln Gly     130 135 140 Val Gln Ser Ser Gly Val Leu Ile Ile Phe Trp Phe Leu Cys Val Val 145 150 155 160 Cys Ala Ile Val Pro Phe Arg Ser Lys Ile Leu Leu Ala Lys Ala Glu                 165 170 175 Gly Glu Ile Ser Asp Pro Phe Arg Phe Thr Thr Phe Tyr Ile His Phe             180 185 190 Ala Leu Val Leu Ser Ala Leu Ile Leu Ala Cys Phe Arg Glu Lys Pro         195 200 205 Pro Phe Phe Ser Ala Lys Asn Val Asp Pro Asn Pro Tyr Pro Glu Thr     210 215 220 Ser Ala Gly Phe Leu Ser Arg Leu Phe Phe Trp Trp Phe Thr Lys Met 225 230 235 240 Ala Ile Tyr Gly Tyr Arg His Pro Leu Glu Glu Lys Asp Leu Trp Ser                 245 250 255 Leu Lys Glu Glu Asp Arg Ser Gln Met Val Val Gln Gln Leu Leu Glu             260 265 270 Ala Trp Arg Lys Gln Glu Lys Gln Thr Ala Arg His Lys Ala Ser Ala         275 280 285 Ala Pro Gly Lys Asn Ala Ser Gly Glu Asp Glu Val Leu Leu Gly Ala     290 295 300 Arg Pro Arg Pro Arg Lys Pro Ser Phe Leu Lys Ala Leu Leu Ala Thr 305 310 315 320 Phe Gly Ser Ser Phe Leu Ile Ser Ala Cys Phe Lys Leu Ile Gln Asp                 325 330 335 Leu Leu Ser Phe Ile Asn Pro Gln Leu Leu Ser Ile Leu Ile Arg Phe             340 345 350 Ile Ser Asn Pro Met Ala Pro Ser Trp Trp Gly Phe Leu Val Ala Gly         355 360 365 Leu Met Phe Leu Cys Ser Met Met Gln Ser Leu Ile Leu Gln His Tyr     370 375 380 Tyr His Tyr Ile Phe Val Thr Gly Val Lys Phe Arg Thr Gly Ile Met 385 390 395 400 Gly Val Ile Tyr Arg Lys Ala Leu Val Ile Thr Asn Ser Val Lys Arg                 405 410 415 Ala Ser Thr Val Gly Glu Ile Val Asn Leu Met Ser Val Asp Ala Gln             420 425 430 Arg Phe Met Asp Leu Ala Pro Phe Leu Asn Leu Leu Trp Ser Ala Pro         435 440 445 Leu Gln Ile Ile Leu Ala Ile Tyr Phe Leu Trp Gln Asn Leu Gly Pro     450 455 460 Ser Val Leu Ala Gly Val Ala Phe Met Val Leu Leu Ile Pro Leu Asn 465 470 475 480 Gly Ala Val Ala Val Lys Met Arg Ala Phe Gln Val Lys Gln Met Lys                 485 490 495 Leu Lys Asp Ser Arg Ile Lys Leu Met Ser Glu Ile Leu Asn Gly Ile             500 505 510 Lys Val Leu Lys Leu Tyr Ala Trp Glu Pro Ser Phe Leu Lys Gln Val         515 520 525 Glu Gly Ile Arg Gln Gly Glu Leu Gln Leu Leu Arg Thr Ala Ala Tyr     530 535 540 Leu His Thr Thr Thr Thr Phe Thr Trp Met Cys Ser Pro Phe Leu Val 545 550 555 560 Thr Leu Ile Thr Leu Trp Val Tyr Val Tyr Val Asp Pro Asn Asn Val                 565 570 575 Leu Asp Ala Glu Lys Ala Phe Val Ser Val Ser Leu Phe Asn Ile Leu             580 585 590 Arg Leu Pro Leu Asn Met Leu Pro Gln Leu Ile Ser Asn Leu Thr Gln         595 600 605 Ala Ser Val Ser Leu Lys Arg Ile Gln Gln Phe Leu Ser Gln Glu Glu     610 615 620 Leu Asp Pro Gln Ser Val Glu Arg Lys Thr Ile Ser Pro Gly Tyr Ala 625 630 635 640 Ile Thr Ile His Ser Gly Thr Phe Thr Trp Ala Gln Asp Leu Pro Pro                 645 650 655 Thr Leu His Ser Leu Asp Ile Gln Val Pro Lys Gly Ala Leu Val Ala             660 665 670 Val Val Gly Pro Val Gly Cys Gly Lys Ser Ser Leu Val Ser Ala Leu         675 680 685 Leu Gly Glu Met Glu Lys Leu Glu Gly Lys Val His Met Lys Gly Ser     690 695 700 Val Ala Tyr Val Pro Gln Gln Ala Trp Ile Gln Asn Cys Thr Leu Gln 705 710 715 720 Glu Asn Val Leu Phe Gly Lys Ala Leu Asn Pro Lys Arg Tyr Gln Gln                 725 730 735 Thr Leu Glu Ala Cys Ala Leu Leu Ala Asp Leu Glu Met Leu Pro Gly             740 745 750 Gly Asp Gln Thr Glu Ile Gly Glu Lys Gly Ile Asn Leu Ser Gly Gly         755 760 765 Gln Arg Gln Arg Val Ser Leu Ala Arg Ala Val Tyr Ser Asp Ala Asp     770 775 780 Ile Phe Leu Leu Asp Asp Pro Leu Ser Ala Val Asp Ser His Val Ala 785 790 795 800 Lys His Ile Phe Asp His Val Ile Gly Pro Glu Gly Val Leu Ala Gly                 805 810 815 Lys Thr Arg Val Leu Val Thr His Gly Ile Ser Phe Leu Pro Gln Thr             820 825 830 Asp Phe Ile Ile Val Leu Ala Asp Gly Gln Val Ser Glu Met Gly Pro         835 840 845 Tyr Pro Ala Leu Leu Gln Arg Asn Gly Ser Phe Ala Asn Phe Leu Cys     850 855 860 Asn Tyr Ala Pro Asp Glu Asp Gln Gly His Leu Glu Asp Ser Trp Thr 865 870 875 880 Ala Leu Glu Gly Ala Glu Asp Lys Glu Ala Leu Leu Ile Glu Asp Thr                 885 890 895 Leu Ser Asn His Thr Asp Leu Thr Asp Asn Asp Pro Val Thr Tyr Val             900 905 910 Val Gln Lys Gln Phe Met Arg Gln Leu Ser Ala Leu Ser Ser Asp Gly         915 920 925 Glu Gly Gln Gly Arg Pro Val Pro Arg Arg His Leu Gly Pro Ser Glu     930 935 940 Lys Val Gln Val Thr Glu Ala Lys Ala Asp Gly Ala Leu Thr Gln Glu 945 950 955 960 Glu Lys Ala Ala Ile Gly Thr Val Glu Leu Ser Val Phe Trp Asp Tyr                 965 970 975 Ala Lys Ala Val Gly Leu Cys Thr Thr Leu Ala Ile Cys Leu Leu Tyr             980 985 990 Val Gly Gln Ser Ala Ala Ala Ile Gly Ala Asn Val Trp Leu Ser Ala         995 1000 1005 Trp Thr Asn Asp Ala Met Ala Asp Ser Arg Gln Asn Asn Thr Ser Leu    1010 1015 1020 Arg Leu Gly Val Tyr Ala Ala Leu Gly Ile Leu Gln Gly Phe Leu Val 1025 1030 1035 1040 Met Leu Ala Ala Met Ala Met Ala Ala Gly Gly Ile Gln Ala Ala Arg                1045 1050 1055 Val Leu His Gln Ala Leu Leu His Asn Lys Ile Arg Ser Pro Gln Ser            1060 1065 1070 Phe Phe Asp Thr Thr Pro Ser Gly Arg Ile Leu Asn Cys Phe Ser Lys        1075 1080 1085 Asp Ile Tyr Val Val Asp Glu Val Leu Ala Pro Val Ile Leu Met Leu    1090 1095 1100 Leu Asn Ser Phe Phe Asn Ala Ile Ser Thr Leu Val Val Ile Met Ala 1105 1110 1115 1120 Ser Thr Pro Leu Phe Thr Val Val Ile Leu Pro Leu Ala Val Leu Tyr                1125 1130 1135 Thr Leu Val Gln Arg Phe Tyr Ala Ala Thr Ser Arg Gln Leu Lys Arg            1140 1145 1150 Leu Glu Ser Val Ser Arg Ser Pro Ile Tyr Ser His Phe Ser Glu Thr        1155 1160 1165 Val Thr Gly Ala Ser Val Ile Arg Ala Tyr Asn Arg Ser Arg Asp Phe    1170 1175 1180 Glu Ile Ile Ser Asp Thr Lys Val Asp Ala Asn Gln Arg Ser Cys Tyr 1185 1190 1195 1200 Pro Tyr Ile Ile Ser Asn Arg Trp Leu Ser Ile Gly Val Glu Phe Val                1205 1210 1215 Gly Asn Cys Val Val Leu Phe Ala Ala Leu Phe Ala Val Ile Gly Arg            1220 1225 1230 Ser Ser Leu Asn Pro Gly Leu Val Gly Leu Ser Val Ser Tyr Ser Leu        1235 1240 1245 Gln Val Thr Phe Ala Leu Asn Trp Met Ile Arg Met Met Ser Asp Leu    1250 1255 1260 Glu Ser Asn Ile Val Ala Val Glu Arg Val Lys Glu Tyr Ser Lys Thr 1265 1270 1275 1280 Glu Thr Glu Ala Pro Trp Val Val Glu Gly Ser Arg Pro Pro Glu Gly                1285 1290 1295 Trp Pro Pro Arg Gly Glu Val Glu Phe Arg Asn Tyr Ser Val Arg Tyr            1300 1305 1310 Arg Pro Gly Leu Asp Leu Val Leu Arg Asp Leu Ser Leu His Val His        1315 1320 1325 Gly Gly Glu Lys Val Gly Ile Val Gly Arg Thr Gly Ala Gly Lys Ser    1330 1335 1340 Ser Met Thr Leu Cys Leu Phe Arg Ile Leu Glu Ala Ala Lys Gly Glu 1345 1350 1355 1360 Ile Arg Ile Asp Gly Leu Asn Val Ala Asp Ile Gly Leu His Asp Leu                1365 1370 1375 Arg Ser Gln Leu Thr Ile Ile Pro Gln Asp Pro Ile Leu Phe Ser Gly            1380 1385 1390 Thr Leu Arg Met Asn Leu Asp Pro Phe Gly Ser Tyr Ser Glu Glu Asp        1395 1400 1405 Ile Trp Trp Ala Leu Glu Leu Ser His Leu His Thr Phe Val Ser Ser    1410 1415 1420 Gln Pro Ala Gly Leu Asp Phe Gln Cys Ser Glu Gly Gly Glu Asn Leu 1425 1430 1435 1440 Ser Val Gly Gln Arg Gln Leu Val Cys Leu Ala Arg Ala Leu Leu Arg                1445 1450 1455 Lys Ser Arg Ile Leu Val Leu Asp Glu Ala Thr Ala Ala Ile Asp Leu            1460 1465 1470 Glu Thr Asp Asn Leu Ile Gln Ala Thr Ile Arg Thr Gln Phe Asp Thr        1475 1480 1485 Cys Thr Val Leu Thr Ile Ala His Arg Leu Asn Thr Ile Met Asp Tyr    1490 1495 1500 Thr Arg Val Leu Val Leu Asp Lys Gly Val Val Ala Glu Phe Asp Ser 1505 1510 1515 1520 Pro Ala Asn Leu Ile Ala Ala Arg Gly Ile Phe Tyr Gly Met Ala Arg                1525 1530 1535 Asp Ala Gly Leu Ala            1540       <210> 19 <211> 18 <212> PRT <213> Homo sapiens    <400> 19 Asn Ile Phe Leu Arg Phe Pro Pro Gly Leu Ser Trp Phe Ser Ser Gly   1 5 10 15 Arg Lys       <210> 20 <211> 22 <212> PRT <213> Homo sapiens    <400> 20 His Gln Ile Cys Pro Gln Asn Gly Leu Asp Ser Lys His Trp Gly His   1 5 10 15 Leu Lys Ile Leu His Leu              20       <210> 21 <211> 12 <212> PRT <213> Homo sapiens    <400> 21 Ser Ala Leu Gln Gly Asn Cys Ala Glu Cys Phe Arg   1 5 10       <210> 22 <211> 21 <212> PRT <213> Homo sapiens    <400> 22 Gly Asn Asp Pro Gln Val Val Asn Asp Thr Pro Lys Val Thr Ala Ser   1 5 10 15 Leu Ser Gln Leu Asp              20       <210> 23 <211> 24 <212> PRT <213> Homo sapiens    <400> 23 Ser Pro Val Ser Arg Phe Pro Thr Glu Cys Tyr Leu His Thr Ala Leu   1 5 10 15 Phe Ser Asn Asn Asp Phe Met Lys              20       <210> 24 <211> 5 <212> PRT <213> Homo sapiens    <400> 24 Lys Lys Lys Lys Lys   1 5          <210> 25 <211> 135 <212> PRT <213> Homo sapiens    <400> 25 Ser Asp Arg Ala Arg Leu Pro Cys Ser Arg Ala Pro Ala Pro Trp Thr   1 5 10 15 Pro Cys Ala Val Pro Gly Ser Ser Ala Pro Ser Ser Gly Thr Pro Thr              20 25 30 Cys Leu Cys Thr Gln Lys Thr Arg Thr Ser Leu Pro Ala Ser Arg Thr          35 40 45 Pro Cys Trp Pro Gly Cys Pro Ala Ser Thr Cys Gly Ser Pro Cys Pro      50 55 60 Ala Thr Cys Ser Thr Cys Gly Thr Ile Val Val Ala Thr Ser Ser Ser  65 70 75 80 Pro Thr Cys Pro Ser Ser Arg Trp Ser Trp Val Ser Cys Cys Gly Ala                  85 90 95 Ser Pro Gly Arg Thr Phe Phe Thr Pro Ser Met Ala Trp Ser Met Ala             100 105 110 Gly Pro Leu Pro Leu Phe Ser Leu Ser Pro Trp Trp Trp Gly Ser         115 120 125 Pro Cys Cys Trp Pro Pro Cys     130 135       <210> 26 <211> 35 <212> PRT <213> Homo sapiens    <400> 26 Tyr Ser Met Ser Gly Cys Arg Ala Tyr Ser Leu Arg Gly Ser Ser Leu   1 5 10 15 Ser Ser Gly Ser Cys Val Trp Ser Ala Pro Ser Ser His Ser Ala Pro              20 25 30 Arg Ser Phe          35       <210> 27 <211> 84 <212> PRT <213> Homo sapiens    <400> 27 Pro Arg Gln Arg Val Arg Ser Gln Thr Pro Ser Ala Ser Pro Pro Ser   1 5 10 15 Thr Ser Thr Leu Pro Trp Tyr Ser Leu Pro Ser Ser Trp Pro Ala Ser              20 25 30 Gly Arg Asn Leu His Phe Ser Pro Gln Arg Met Ser Thr Leu Thr Pro          35 40 45 Thr Leu Arg Pro Ala Leu Ala Phe Ser Pro Ala Cys Phe Ser Gly Gly      50 55 60 Ser Gln Arg Trp Pro Ser Met Ala Thr Gly Ile Pro Trp Arg Arg Arg  65 70 75 80 Thr Ser Gly Pro       <210> 28 <211> 56 <212> PRT <213> Homo sapiens    <400> 28 Arg Lys Arg Thr Asp Pro Arg Trp Trp Cys Ser Ser Cys Trp Arg His   1 5 10 15 Gly Gly Ser Arg Lys Ser Arg Arg His Asp Thr Arg Leu Gln Gln His              20 25 30 Leu Gly Lys Met Pro Pro Ala Arg Thr Arg Cys Cys Trp Val Pro Gly          35 40 45 Pro Gly Pro Gly Ser Pro Pro Ser      50 55       <210> 29 <211> 34 <212> PRT <213> Homo sapiens    <400> 29 Arg Pro Cys Trp Pro Pro Ser Ala Pro Ala Ser Ser Ser Val Pro Ala   1 5 10 15 Ser Ser Leu Ser Arg Thr Cys Ser Pro Ser Ser Ile His Ser Cys Ser              20 25 30 Ala Ser       <210> 30 <211> 19 <212> PRT <213> Homo sapiens    <400> 30 Ser Gly Leu Ser Pro Thr Pro Trp Pro Pro Pro Gly Gly Ala Ser Trp   1 5 10 15 Trp Leu Gly       <210> 31 <211> 5 <212> PRT <213> Homo sapiens    <400> 31 Cys Ser Cys Ala Pro   1 5       <210> 32 <211> 10 <212> PRT <213> Homo sapiens    <400> 32 Ser Tyr Asn Thr Ile Thr Thr Thr Ser Leu   1 5 10       <210> 33 <211> 68 <212> PRT <213> Homo sapiens    <400> 33 Ser Phe Val Leu Gly Ser Trp Val Ser Ser Thr Gly Arg Leu Trp Leu   1 5 10 15 Ser Pro Thr Gln Ser Asn Val Arg Pro Leu Trp Gly Lys Leu Ser Thr              20 25 30 Ser Cys Gln Trp Met Pro Ser Ala Ser Trp Thr Leu Pro Pro Ser Ser          35 40 45 Ile Cys Cys Gly Gln His Pro Cys Arg Ser Ser Trp Arg Ser Thr Ser      50 55 60 Ser Gly Arg Thr  65       <210> 34 <211> 13 <212> PRT <213> Homo sapiens    <400> 34 Val Pro Leu Ser Trp Leu Glu Ser Leu Ser Trp Ser Cys   1 5 10       <210> 35 <211> 8 <212> PRT <213> Homo sapiens    <400> 35 Phe His Ser Thr Glu Leu Trp Pro   1 5       <210> 36 <211> 6 <212> PRT <213> Homo sapiens    <400> 36 Arg Cys Ala Pro Ser Arg   1 5       <210> 37 <211> 6 <212> PRT <213> Homo sapiens    <400> 37 Arg Thr Arg Ala Ser Ser   1 5          <210> 38 <211> 5 <212> PRT <213> Homo sapiens    <400> 38 Thr Ala Ser Arg Cys   1 5       <210> 39 <211> 9 <212> PRT <213> Homo sapiens    <400> 39 Ser Cys Thr Pro Gly Ser Pro Ala Ser   1 5       <210> 40 <211> 34 <212> PRT <213> Homo sapiens    <400> 40 Ser Arg Trp Arg Ala Ser Gly Arg Val Ser Ser Ser Cys Cys Ala Arg   1 5 10 15 Arg Pro Thr Ser Thr Pro Gln Pro Pro Ser Pro Gly Cys Ala Ala Pro              20 25 30 Ser Trp       <210> 41 <211> 29 <212> PRT <213> Homo sapiens    <400> 41 Ser Pro Ser Gly Cys Thr Cys Thr Trp Thr Gln Thr Met Cys Trp Thr   1 5 10 15 Pro Arg Arg Pro Leu Cys Leu Cys Pro Cys Leu Ile Ser              20 25       <210> 42 <211> 9 <212> PRT <213> Homo sapiens    <400> 42 Asp Phe Pro Ser Thr Cys Cys Pro Ser   1 5       <210> 43 <211> 6 <212> PRT <213> Homo sapiens    <400> 43 Leu Arg Pro Val Cys Leu   1 5       <210> 44 <211> 6 <212> PRT <213> Homo sapiens    <400> 44 Asn Gly Ser Ser Asn Ser   1 5       <210> 45 <211> 40 <212> PRT <213> Homo sapiens    <400> 45 Ala Lys Arg Asn Leu Thr Pro Arg Val Trp Lys Glu Arg Pro Ser Pro   1 5 10 15 Gln Ala Met Pro Ser Pro Tyr Thr Val Ala Pro Ser Pro Gly Pro Arg              20 25 30 Thr Cys Pro Pro Leu Cys Thr Ala          35 40       <210> 46 <211> 33 <212> PRT <213> Homo sapiens    <400> 46 Thr Ser Arg Ser Arg Lys Gly His Trp Trp Pro Trp Trp Gly Leu Trp   1 5 10 15 Ala Val Gly Ser Pro Pro Trp Cys Leu Pro Cys Trp Glu Arg Trp Arg              20 25 30 Ser       <210> 47 <211> 5 <212> PRT <213> Homo sapiens    <400> 47 Lys Ala Lys Cys Thr   1 5       <210> 48 <211> 27 <212> PRT <213> Homo sapiens    <400> 48 Arg Ala Pro Trp Pro Met Cys Pro Ser Arg His Gly Ser Arg Thr Ala   1 5 10 15 Leu Phe Arg Lys Thr Cys Phe Ser Ala Lys Pro              20 25       <210> 49 <211> 14 <212> PRT <213> Homo sapiens    <400> 49 Thr Pro Ser Ala Thr Ser Arg Leu Trp Arg Pro Val Pro Cys   1 5 10       <210> 50 <211> 77 <212> PRT <213> Homo sapiens    <400> 50 Leu Thr Trp Arg Cys Cys Leu Val Gly Ile Arg Gln Arg Leu Glu Arg   1 5 10 15 Arg Ala Leu Thr Cys Leu Gly Ala Ser Gly Ser Gly Ser Val Trp Leu              20 25 30 Glu Leu Phe Thr Val Met Pro Ile Phe Ser Cys Trp Met Thr His Cys          35 40 45 Pro Arg Trp Thr Leu Met Trp Pro Ser Thr Ser Leu Thr Thr Ser Ser      50 55 60 Gly Gln Lys Ala Cys Trp Gln Ala Arg Arg Glu Cys Trp  65 70 75       <210> 51 <211> 15 <212> PRT <213> Homo sapiens    <400> 51 Arg Thr Ala Leu Ala Ser Cys Pro Arg Gln Thr Ser Ser Leu Cys   1 5 10 15       <210> 52 <211> 53 <212> PRT <213> Homo sapiens    <400> 52 Leu Met Asp Arg Cys Leu Arg Trp Ala Arg Thr Gln Pro Cys Cys Ser   1 5 10 15 Ala Thr Ala Pro Leu Pro Thr Phe Ser Ala Thr Met Pro Pro Met Arg              20 25 30 Thr Lys Gly Thr Trp Arg Thr Ala Gly Pro Arg Trp Lys Val Gln Arg          35 40 45 Ile Arg Arg His Cys      50       <210> 53 <211> 10 <212> PRT <213> Homo sapiens    <400> 53 Leu Lys Thr His Ser Ala Thr Thr Arg Ile   1 5 10       <210> 54 <211> 14 <212> PRT <213> Homo sapiens    <400> 54 Gln Thr Met Ile Gln Ser Pro Met Trp Ser Arg Ser Ser Leu   1 5 10       <210> 55 <211> 26 <212> PRT <213> Homo sapiens    <400> 55 Val Pro Cys Pro Gln Met Gly Arg Asp Arg Val Gly Leu Tyr Pro Gly   1 5 10 15 Gly Thr Trp Val His Gln Arg Arg Cys Arg              20 25       <210> 56 <211> 8 <212> PRT <213> Homo sapiens    <400> 56 Gln Arg Arg Arg Gln Met Gly His   1 5       <210> 57 <211> 66 <212> PRT <213> Homo sapiens    <400> 57 Pro Arg Arg Arg Lys Gln Pro Leu Ala Leu Trp Ser Ser Val Cys Ser   1 5 10 15 Gly Ile Met Pro Arg Pro Trp Gly Ser Val Pro Arg Trp Pro Ser Val              20 25 30 Ser Cys Met Trp Val Lys Val Arg Leu Pro Leu Glu Pro Met Cys Gly          35 40 45 Ser Val Pro Gly Gln Met Met Pro Trp Gln Thr Val Asp Arg Thr Thr      50 55 60 Leu Pro  65       <210> 58 <211> 7 <212> PRT <213> Homo sapiens    <400> 58 Gly Trp Ala Ser Met Leu Leu   1 5       <210> 59 <211> 7 <212> PRT <213> Homo sapiens    <400> 59 Glu Phe Cys Lys Gly Ser Trp   1 5       <210> 60 <211> 42 <212> PRT <213> Homo sapiens    <400> 60 Cys Trp Gln Pro Trp Pro Trp Gln Arg Val Ala Ser Arg Leu Pro Val   1 5 10 15 Cys Cys Thr Arg His Cys Cys Thr Thr Arg Tyr Ala Arg His Ser Pro              20 25 30 Ser Leu Thr Pro His His Gln Ala Ala Ser          35 40       <210> 61 <211> 54 <212> PRT <213> Homo sapiens    <400> 61 Thr Ala Ser Pro Arg Thr Ser Met Ser Leu Met Arg Phe Trp Pro Leu   1 5 10 15 Ser Ser Ser Cys Cys Ser Ile Pro Ser Ser Thr Pro Ser Pro Leu Leu              20 25 30 Trp Ser Ser Trp Pro Ala Arg Arg Ser Ser Leu Trp Ser Ser Cys Pro          35 40 45 Trp Leu Cys Ser Thr Pro      50       <210> 62 <211> 11 <212> PRT <213> Homo sapiens    <400> 62 Cys Ser Ala Ser Met Gln Pro His His Gly Asn   1 5 10       <210> 63 <211> 18 <212> PRT <213> Homo sapiens    <400> 63 Ser Gly Trp Asn Gln Ser Ala Ala His Leu Ser Thr Pro Thr Phe Arg   1 5 10 15 Arg Gln       <210> 64 <211> 39 <212> PRT <213> Homo sapiens    <400> 64 Leu Val Pro Val Ser Ser Gly Pro Thr Thr Ala Ala Gly Ile Leu Arg   1 5 10 15 Ser Ser Val Ile Leu Arg Trp Met Pro Thr Arg Glu Ala Ala Thr Pro              20 25 30 Thr Ser Ser Pro Thr Gly Gly          35       <210> 65 <211> 25 <212> PRT <213> Homo sapiens    <400> 65 Ala Ser Glu Trp Ser Ser Trp Gly Thr Ala Trp Cys Ser Leu Leu His   1 5 10 15 Tyr Leu Pro Ser Ser Gly Gly Ala Ala              20 25       <210> 66 <211> 14 <212> PRT <213> Homo sapiens    <400> 66 Thr Arg Gly Trp Trp Ala Phe Leu Cys Pro Thr Pro Cys Arg   1 5 10       <210> 67 <211> 55 <212> PRT <213> Homo sapiens    <400> 67 Cys Gln Ile Trp Asn Leu Thr Ser Trp Leu Trp Arg Gly Ser Arg Ser   1 5 10 15 Thr Pro Arg Gln Arg Gln Arg Arg Pro Gly Trp Trp Lys Ala Ala Ala              20 25 30 Leu Pro Lys Val Gly Pro His Val Gly Arg Trp Ser Ser Gly Ile Ile          35 40 45 Leu Cys Ala Thr Gly Arg Ala      50 55       <210> 68 <211> 22 <212> PRT <213> Homo sapiens    <400> 68 Val Cys Met Cys Thr Val Ala Arg Arg Trp Gly Ser Trp Ala Ala Leu   1 5 10 15 Gly Leu Ala Ser Leu Pro              20       <210> 69 <211> 33 <212> PRT <213> Homo sapiens    <400> 69 Pro Phe Ala Cys Ser Ala Ser Trp Arg Arg Gln Arg Val Lys Ser Ala   1 5 10 15 Leu Met Ala Ser Met Trp Gln Thr Ser Ala Ser Met Thr Cys Ala Leu              20 25 30 Ser       <210> 70 <211> 15 <212> PRT <213> Homo sapiens    <400> 70 Pro Ser Ser Arg Arg Thr Pro Ser Cys Ser Arg Gly Pro Cys Ala   1 5 10 15       <210> 71 <211> 25 <212> PRT <213> Homo sapiens    <400> 71 Thr Trp Thr Pro Ser Ala Ala Thr Gln Arg Arg Thr Phe Gly Gly Leu   1 5 10 15 Trp Ser Cys Pro Thr Cys Thr Arg Leu              20 25       <210> 72 <211> 40 <212> PRT <213> Homo sapiens    <400> 72 Ala Pro Ser Arg Gln Ala Trp Thr Ser Ser Ala Gln Arg Ala Gly Arg   1 5 10 15 Ile Ser Ala Trp Ala Arg Gly Ser Ser Cys Ala Trp Pro Glu Pro Cys              20 25 30 Ser Ala Arg Ala Ala Ser Trp Phe          35 40       <210> 73 <211> 28 <212> PRT <213> Homo sapiens    <400> 73 Thr Arg Pro Gln Leu Pro Ser Thr Trp Arg Leu Thr Thr Ser Ser Arg   1 5 10 15 Leu Pro Ser Ala Pro Ser Leu Ile Pro Ala Leu Ser              20 25       <210> 74 <211> 21 <212> PRT <213> Homo sapiens    <400> 74 Pro Ser His Thr Gly Leu Thr Leu Ser Trp Thr Thr Pro Gly Ser Trp   1 5 10 15 Ser Trp Thr Lys Glu              20       <210> 75 <211> 30 <212> PRT <213> Homo sapiens    <400> 75 Leu Asn Leu Ile Leu Gln Pro Thr Ser Leu Gln Leu Glu Ala Ser Ser   1 5 10 15 Thr Gly Trp Pro Glu Met Leu Asp Leu Pro Lys Ile Tyr Ser              20 25 30       <210> 76 <211> 57 <212> PRT <213> Homo sapiens    <400> 76 Asp Phe Leu Leu Ala Phe Pro Gly Phe His Gln Glu Gly Asn Asp Thr   1 5 10 15 Lys Tyr Val Arg Arg Met Asp Leu Ile Ala Asn Thr Gly Gly Thr Leu              20 25 30 Arg Phe Cys Thr Cys Lys Val Pro Tyr Arg Val Thr Val Leu Asn Ala          35 40 45 Leu Asp Glu Glu Met Ile Pro Lys Trp      50 55       <210> 77 <211> 9 <212> PRT <213> Homo sapiens    <400> 77 Met Thr Arg Leu Arg Ser Gln Leu Val   1 5       <210> 78 <211> 24 <212> PRT <213> Homo sapiens    <400> 78 Thr Ser Pro Arg Ser Pro Asp Ser Gln Leu Ser Val Ile Cys Thr Leu   1 5 10 15 His Cys Phe Gln Ile Thr Ile Leu              20       <210> 79 <211> 7 <212> PRT <213> Homo sapiens    <400> 79 Asn Glu Lys Lys Lys Lys Lys   1 5       <210> 80 <211> 138 <212> PRT <213> Homo sapiens    <400> 80 Pro Thr Ala Leu Ala Phe Leu Ala Ala Ala Pro Arg Pro His Gly Arg   1 5 10 15 Pro Val Arg Phe Arg Gly Ala Arg Leu Gln Val Leu Gly Leu Gln Pro              20 25 30 Val Cys Ala His Arg Lys Pro Gly Pro His Ser Leu Leu Pro Glu Leu          35 40 45 Pro Ala Gly Leu Gly Ala Pro His Leu Pro Val Gly Arg Pro Ala Leu      50 55 60 Leu Leu Ala Leu Pro Ala Ala Pro Leu Ser Trp Leu His His Pro Leu  65 70 75 80 Pro Pro Val Gln Ala Gln Asp Gly Pro Gly Cys Pro Ala Val Val Arg                  85 90 95 Leu Leu Gly Gly Pro Phe Leu Leu Leu Pro Trp Pro Gly Pro Trp Pro             100 105 110 Gly Pro Cys Pro Cys Phe Leu Cys His Pro Leu Gly Gly Gly Gly His         115 120 125 His Ala Ala Gly His Pro Ala Asp Thr Val     130 135       <210> 81 <211> 37 <212> PRT <213> Homo sapiens    <400> 3 Ala Ala Ala Gly Arg Thr Val Phe Gly Gly Pro His Tyr Leu Leu Val   1 5 10 15 Pro Val Cys Gly Leu Arg His Arg Pro Ile Pro Leu Gln Asp Pro Phe              20 25 30 Ser Gln Gly Arg Gly          35       <210> 82 <211> 40 <212> PRT <213> Homo sapiens    <400> 82 Asp Leu Arg Pro Leu Pro Leu His His Leu Leu His Pro Leu Cys Pro   1 5 10 15 Gly Thr Leu Cys Pro His Leu Gly Leu Leu Gln Gly Glu Thr Ser Ile              20 25 30 Phe Leu Arg Lys Glu Cys Arg Pro          35 40       <210> 83 <211> 283 <212> PRT <213> Homo sapiens    <400> 83 Asp Gln Arg Trp Leu Ser Leu Pro Pro Val Phe Leu Val Val His Lys   1 5 10 15 Asp Gly His Leu Trp Leu Pro Ala Ser Pro Gly Gly Glu Gly Pro Leu              20 25 30 Val Pro Lys Gly Arg Gly Gln Ile Pro Asp Gly Gly Ala Ala Ala Ala          35 40 45 Gly Gly Met Glu Glu Ala Gly Lys Ala Asp Gly Thr Thr Gln Gly Phe      50 55 60 Ser Ser Thr Trp Glu Lys Cys Leu Arg Arg Gly Arg Gly Ala Ala Gly  65 70 75 80 Cys Pro Ala Gln Ala Pro Glu Ala Leu Leu Pro Glu Gly Pro Ala Gly                  85 90 95 His Leu Arg Leu Gln Leu Pro His Gln Cys Leu Leu Gln Ala Tyr Pro             100 105 110 Gly Pro Ala Leu Leu His Gln Ser Thr Ala Ala Gln His Pro Asp Gln         115 120 125 Val Tyr Leu Gln Pro His Gly Pro Leu Leu Val Gly Leu Pro Gly Gly     130 135 140 Trp Ala Asp Val Pro Val Leu His Asp Ala Val Ala Asp Leu Thr Thr 145 150 155 160 Leu Leu Pro Leu His Leu Cys Asp Trp Gly Glu Val Ser Tyr Trp Asp                 165 170 175 His Gly Cys His Leu Gln Glu Gly Ser Gly Tyr His Gln Leu Ser Gln             180 185 190 Thr Cys Val His Cys Gly Gly Asn Cys Gln Pro His Val Ser Gly Cys         195 200 205 Pro Ala Leu His Gly Pro Cys Pro Leu Pro Gln Ser Ala Val Val Ser     210 215 220 Thr Pro Ala Asp His Pro Gly Asp Leu Leu Pro Leu Ala Glu Pro Arg 225 230 235 240 Ser Leu Cys Pro Gly Trp Ser Arg Phe His Gly Leu Ala Asp Ser Thr                 245 250 255 Gln Arg Ser Cys Gly Arg Glu Asp Ala Arg Leu Pro Gly Lys Ala Asn             260 265 270 Glu Ile Glu Gly Leu Ala His Gln Ala Asp Glu         275 280       <210> 84 <211> 27 <212> PRT <213> Homo sapiens    <400> 84 Asp Pro Glu Arg His Gln Gly Ala Glu Ala Val Arg Leu Gly Ala Gln   1 5 10 15 Leu Pro Glu Ala Gly Gly Gly His Gln Ala Gly              20 25       <210> 85 <211> 54 <212> PRT <213> Homo sapiens    <400> 85 Ala Pro Ala Ala Ala His Gly Gly Leu Pro Pro His His Asn His Leu   1 5 10 15 His Leu Asp Val Gln Pro Leu Pro Gly Asp Pro Asp His Pro Leu Gly              20 25 30 Val Arg Val Arg Gly Pro Lys Gln Cys Ala Gly Arg Arg Glu Gly Leu          35 40 45 Cys Val Cys Val Leu Val      50       <210> 86 <211> 35 <212> PRT <213> Homo sapiens    <400> 86 Tyr Leu Lys Thr Ser Pro Gln His Ala Ala Pro Val Asn Gln Gln Pro   1 5 10 15 Asp Ser Gly Gln Cys Val Ser Glu Thr Asp Pro Ala Ile Pro Glu Pro              20 25 30 Arg Gly Thr          35       <210> 87 <211> 119 <212> PRT <213> Homo sapiens    <400> 87 Pro Pro Glu Cys Gly Lys Lys Asp His Leu Pro Arg Leu Cys His His   1 5 10 15 His Thr Gln Trp His Leu His Leu Gly Pro Gly Pro Ala Pro His Ser              20 25 30 Ala Gln Pro Arg His Pro Gly Pro Glu Arg Gly Thr Gly Gly Arg Gly          35 40 45 Gly Ala Cys Gly Leu Trp Glu Val Leu Pro Gly Val Cys Pro Ala Gly      50 55 60 Arg Asp Gly Glu Ala Arg Arg Gln Ser Ala His Glu Gly Leu Arg Gly  65 70 75 80 Leu Cys Ala Pro Ala Gly Met Asp Pro Glu Leu His Ser Ser Gly Lys                  85 90 95 Arg Ala Phe Arg Gln Ser Pro Glu Pro Gln Ala Leu Pro Ala Asp Ser             100 105 110 Gly Gly Leu Cys Leu Ala Ser         115       <210> 88 <211> 17 <212> PRT <213> Homo sapiens    <400> 88 Pro Gly Asp Ala Ala Trp Trp Gly Ser Asp Arg Asp Trp Arg Glu Gly   1 5 10 15 His       <210> 89 <211> 17 <212> PRT <213> Homo sapiens    <400> 89 Pro Val Trp Gly Pro Ala Ala Ala Gly Gln Ser Gly Ser Ser Cys Leu   1 5 10 15 Gln       <210> 90 <211> 7 <212> PRT <213> Homo sapiens    <400> 90 Cys Arg Tyr Phe Leu Ala Gly   1 5       <210> 91 <211> 14 <212> PRT <213> Homo sapiens    <400> 91 Pro Thr Val Arg Gly Gly Leu Ser Cys Gly Gln Ala His Leu   1 5 10       <210> 92 <211> 21 <212> PRT <213> Homo sapiens    <400> 92 Pro Arg His Arg Ala Arg Arg Arg Ala Gly Arg Gln Asp Ala Ser Ala   1 5 10 15 Gly Asp Ala Arg His              20       <210> 93 <211> 12 <212> PRT <213> Homo sapiens    <400> 93 Leu Pro Ala Pro Asp Arg Leu His His Cys Ala Ser   1 5 10       <210> 94 <211> 24 <212> PRT <213> Homo sapiens    <400> 94 Asp Gly Pro Val Pro Ser Pro Ala Ala Ala Gln Arg Leu Leu Cys Gln   1 5 10 15 Leu Ser Leu Gln Leu Cys Pro Arg              20       <210> 95 <211> 17 <212> PRT <213> Homo sapiens    <400> 95 Gly Pro Arg Ala Pro Gly Gly Gln Leu Asp Arg Val Gly Arg Cys Arg   1 5 10 15 Gly       <210> 96 <211> 5 <212> PRT <213> Homo sapiens    <400> 96 Gly Gly Thr Ala Asp   1 5       <210> 97 <211> 12 <212> PRT <213> Homo sapiens    <400> 97 Arg His Thr Gln Gln Pro His Gly Ser Asp Arg Gln   1 5 10       <210> 98 <211> 104 <212> PRT <213> Homo sapiens    <400> 98 Ser Ser His Leu Cys Gly Pro Glu Ala Val Tyr Glu Thr Ala Glu Cys   1 5 10 15 Pro Val Leu Arg Trp Gly Gly Thr Gly Ser Ala Cys Thr Pro Glu Ala              20 25 30 Pro Gly Ser Ile Arg Glu Gly Ala Gly Asp Arg Gly Glu Gly Arg Trp          35 40 45 Gly Thr Asp Pro Gly Gly Glu Ser Ser His Trp His Cys Gly Ala Gln      50 55 60 Cys Val Leu Gly Leu Cys Gln Gly Arg Gly Ala Leu Tyr His Ala Gly  65 70 75 80 His Leu Ser Pro Val Cys Gly Ser Lys Cys Gly Cys His Trp Ser Gln                  85 90 95 Cys Val Ala Gln Cys Leu Asp Lys             100       <210> 99 <211> 5 <212> PRT <213> Homo sapiens    <400> 99 Cys His Gly Arg Gln   1 5       <210> 100 <211> 56 <212> PRT <213> Homo sapiens    <400> 100 Thr Glu Gln His Phe Pro Glu Ala Gly Arg Leu Cys Cys Phe Arg Asn   1 5 10 15 Ser Ala Arg Val Leu Gly Asp Ala Gly Ser His Gly His Gly Ser Gly              20 25 30 Trp His Pro Gly Cys Pro Cys Val Ala Pro Gly Thr Ala Ala Gln Gln          35 40 45 Asp Thr Leu Ala Thr Val Leu Leu      50 55       <210> 101 <211> 18 <212> PRT <213> Homo sapiens    <400> 101 His His Thr Ile Arg Pro His Pro Glu Leu Leu Leu Gln Gly His Leu   1 5 10 15 Cys Arg       <210> 102 <211> 89 <212> PRT <213> Homo sapiens    <400> 102 Gly Ser Gly Pro Cys His Pro His Ala Ala Gln Phe Leu Leu Gln Arg   1 5 10 15 His Leu His Ser Cys Gly His His Gly Gln His Ala Ala Leu His Cys              20 25 30 Gly His Pro Ala Pro Gly Cys Ala Leu His Leu Ser Ala Ala Leu Leu          35 40 45 Cys Ser His Ile Thr Ala Thr Glu Ala Ala Gly Ile Ser Gln Pro Leu      50 55 60 Thr Tyr Leu Leu Pro Leu Phe Gly Asp Ser Asp Trp Cys Gln Cys His  65 70 75 80 Pro Gly Leu Gln Pro Gln Pro Gly Phe                  85       <210> 103 <211> 75 <212> PRT <213> Homo sapiens    <400> 103 Gly Gly Cys Gln Pro Glu Lys Leu Leu Pro Leu His His Leu Gln Pro   1 5 10 15 Val Ala Glu His Arg Ser Gly Val Arg Gly Glu Leu Arg Gly Ala Leu              20 25 30 Cys Cys Thr Ile Cys Arg His Arg Glu Glu Gln Pro Glu Pro Gly Ala          35 40 45 Gly Gly Pro Phe Cys Val Leu Leu Leu Ala Gly Asp Ile Cys Ser Glu      50 55 60 Leu Asp Asp Thr Asn Asp Val Arg Phe Gly Ile  65 70 75       <210> 104 <211> 92 <212> PRT <213> Homo sapiens    <400> 104 His Arg Gly Cys Gly Glu Gly Gln Gly Val Leu Gln Asp Arg Asp Arg   1 5 10 15 Gly Ala Leu Gly Gly Gly Arg Gln Pro Pro Ser Arg Arg Leu Ala Pro              20 25 30 Thr Trp Gly Gly Gly Val Pro Glu Leu Phe Cys Ala Leu Pro Ala Gly          35 40 45 Pro Arg Pro Gly Ala Glu Arg Pro Glu Ser Ala Cys Ala Arg Trp Arg      50 55 60 Glu Gly Gly Asp Arg Gly Pro His Trp Gly Trp Gln Val Phe His Asp  65 70 75 80 Pro Leu Pro Val Pro His Pro Gly Gly Gly Lys Gly                  85 90       <210> 105 <211> 10 <212> PRT <213> Homo sapiens    <400> 105 Trp Pro Gln Cys Gly Arg His Arg Pro Pro   1 5 10       <210> 106 <211> 99 <212> PRT <213> Homo sapiens    <400> 106 Pro Ala Leu Ser Ala Asp His His Pro Ala Gly Pro His Pro Val Leu   1 5 10 15 Gly Asp Pro Ala His Glu Pro Gly Pro Leu Arg Gln Leu Leu Arg Gly              20 25 30 Gly His Leu Val Gly Phe Gly Ala Val Pro Pro Ala His Val Cys Glu          35 40 45 Leu Pro Ala Gly Arg Pro Gly Leu Pro Val Leu Arg Gly Arg Gly Glu      50 55 60 Ser Gln Arg Gly Pro Glu Ala Ala Arg Val Pro Gly Pro Ser Pro Ala  65 70 75 80 Pro Gln Glu Pro His Pro Gly Phe Arg Arg Gly His Ser Cys His Arg                  85 90 95 Pro Gly Asp       <210> 107 <211> 11 <212> PRT <213> Homo sapiens    <400> 107 Gln Pro His Pro Gly Tyr His Pro His Pro Val   1 5 10       <210> 108 <211> 11 <212> PRT <213> Homo sapiens    <400> 108 Tyr Leu His Cys Pro Asp His Arg Thr Pro Ala   1 5 10       <210> 109 <211> 17 <212> PRT <213> Homo sapiens    <400> 109 His Tyr His Gly Leu His Gln Gly Pro Gly Pro Gly Gln Arg Ser Ser   1 5 10 15 Ser       <210> 110 <211> 8 <212> PRT <213> Homo sapiens    <400> 110 Phe Ser Ser Gln Pro His Cys Ser   1 5       <210> 111 <211> 42 <212> PRT <213> Homo sapiens    <400> 111 Arg His Leu Leu Arg Asp Gly Gln Arg Cys Trp Thr Cys Leu Lys Tyr   1 5 10 15 Ile Pro Glu Ile Ser Ser Trp Pro Phe Leu Val Phe Ile Arg Lys Glu              20 25 30 Met Thr Pro Asn Met Ser Ala Glu Trp Thr          35 40       <210> 112 <211> 6 <212> PRT <213> Homo sapiens    <400> 112 Gln Thr Leu Gly Ala Pro   1 5       <210> 113 <211> 10 <212> PRT <213> Homo sapiens    <400> 113 Asp Phe Ala Pro Val Lys Cys Leu Thr Gly   1 5 10       <210> 114 <211> 5 <212> PRT <213> Homo sapiens    <400> 114 Ser Pro Ser Gly Glu   1 5       <210> 115 <211> 14 <212> PRT <213> Homo sapiens    <400> 115 Phe Glu Pro Val Arg Leu Val Pro Gly Leu Pro Ile Pro Asn   1 5 10       <210> 116 <211> 10 <212> PRT <213> Homo sapiens    <400> 116 Val Leu Phe Ala His Cys Thr Val Phe Lys   1 5 10       <210> 117 <211> 10 <212> PRT <213> Homo sapiens    <400> 117 Arg Phe Tyr Glu Met Lys Lys Lys Lys Lys   1 5 10                <210> 118 <211> 16 <212> PRT <213> Homo sapiens    <400> 118 Lys Arg Asp Ile Val Met Arg His Thr Thr Lys Val Ser Met Pro Asn   1 5 10 15       <210> 119 <211> 6 <212> PRT <213> Homo sapiens    <400> 119 Asn Gln Cys Asn Ile Gly   1 5       <210> 120 <211> 11 <212> PRT <213> Homo sapiens    <400> 120 Glu Asn Leu Ile Phe Gln Lys Arg Tyr Ser Thr   1 5 10    <210> 121 <211> 10 <212> PRT <213> Homo sapiens    <400> 121 Arg Ile Leu His Ile Lys Ser Ser Phe Leu   1 5 10       <210> 122 <211> 8 <212> PRT <213> Homo sapiens    <400> 122 Ser Phe Asn Ser Leu Met Tyr Asn   1 5       <210> 123 <211> 11 <212> PRT <213> Homo sapiens    <400> 123 Ala Leu Phe Arg Gln Gly Gly Met Ser Val Ile   1 5 10       <210> 124 <211> 18 <212> PRT <213> Homo sapiens    <400> 124 Val Ile Ile Thr Leu Glu Ser Val Phe Gln Ser Phe Lys Ile Asn Ser   1 5 10 15 Met Pro       <210> 125 <211> 11 <212> PRT <213> Homo sapiens    <400> 125 Lys Ile Lys Ser Lys Ile Asn Val Asn Tyr Phe   1 5 10       <210> 126 <211> 10 <212> PRT <213> Homo sapiens    <400> 126 Leu Ile Ile Thr Met Ser Thr Ser Val Tyr   1 5 10       <210> 127 <211> 11 <212> PRT <213> Homo sapiens    <400> 127 Tyr Leu Leu Trp Glu Ser His Cys Gly Trp His   1 5 10       <210> 128 <211> 5 <212> PRT <213> Homo sapiens    <400> 128 Lys Leu His His Leu   1 5       <210> 129 <211> 33 <212> PRT <213> Homo sapiens    <400> 129 Ser Ser Ile Cys Pro Gln Met Asp Ser Ser Leu Ala Lys Thr Arg Phe   1 5 10 15 Ile Gly Arg His Arg Val Arg Glu Trp Glu Asp Gly Val Glu Ala Gly              20 25 30 Cys       <210> 130 <211> 5 <212> PRT <213> Homo sapiens    <400> 130 Ser Ala Val Ser Glu   1 5       <210> 131 <211> 5 <212> PRT <213> Homo sapiens    <400> 131 Phe Cys Leu Leu Glu   1 5       <210> 132 <211> 32 <212> PRT <213> Homo sapiens    <400> 132 Trp Ser Met Phe Gly Gly Ile Leu Cys Phe Ile Arg Ser Glu Arg Tyr   1 5 10 15 Leu Gln Ser Lys Leu Gln Met Thr His Lys Ser Val Asn Asn Ser Pro              20 25 30       <210> 133 <211> 18 <212> PRT <213> Homo sapiens    <400> 133 Tyr Ala Lys Met Lys Thr Lys His Tyr Cys Tyr Pro Lys Gly Thr Gly   1 5 10 15 Ala Trp       <210> 134 <211> 7 <212> PRT <213> Homo sapiens    <400> 134 Cys Ala Asp Gly Ala Val Gly   1 5       <210> 135 <211> 16 <212> PRT <213> Homo sapiens    <400> 135 Glu Ser Tyr Tyr Arg Phe Ser Leu Leu Gly Phe Ile Gly Gly Ser Tyr   1 5 10 15       <210> 136 <211> 7 <212> PRT <213> Homo sapiens    <400> 136 Asp Glu Ile Val Leu Ser Phe   1 5       <210> 137 <211> 48 <212> PRT <213> Homo sapiens    <400> 137 Ile Gln Ile Ser Cys Leu Glu Leu Val Leu Arg Met Gly Val Ile Lys   1 5 10 15 Glu Phe Phe Val Phe Leu Phe Val Cys Leu Phe Trp Leu Leu Ser Asn              20 25 30 Thr Pro Leu Thr Phe Ile Ser Ile Ile Leu Gln Arg Lys Glu Thr Asn          35 40 45       <210> 138 <211> 50 <212> PRT <213> Homo sapiens    <400> 138 Asn Val Cys Phe Asn Lys His Phe Asn Lys Phe Ser Gly Phe Phe Phe   1 5 10 15 Pro Leu Leu Lys Lys Leu Ala Tyr Thr Ile Ala Ile Lys Glu Leu Met              20 25 30 Leu Thr Ile Val Cys Tyr Asn Leu Ser Asp Phe Ser Lys Glu Ala Gln          35 40 45 Cys His      50       <210> 139 <211> 7 <212> PRT <213> Homo sapiens    <400> 139 Ile Cys Glu Gly Gln Arg Asn   1 5       <210> 140 <211> 35 <212> PRT <213> Homo sapiens    <400> 140 Tyr Phe His Phe Met Ile Phe Thr Leu Val Asn Phe Val Tyr Lys Asn   1 5 10 15 Thr Arg Gln Ser Val Leu Pro Met Glu Thr Gly Phe Arg Leu Leu Cys              20 25 30 Phe Tyr Cys          35       <210> 141 <211> 9 <212> PRT <213> Homo sapiens    <400> 141 Ser Leu Lys Phe Arg Asn Ala Asn Thr   1 5       <210> 142 <211> 11 <212> PRT <213> Homo sapiens    <400> 142 Ile Ser Phe Phe Leu Thr Ile Leu Glu Asp Cys   1 5 10       <210> 143 <211> 7 <212> PRT <213> Homo sapiens    <400> 143 Tyr Phe Asp Ile Phe Leu Ala   1 5       <210> 144 <211> 11 <212> PRT <213> Homo sapiens    <400> 144 Thr Tyr Leu Gln Ile Cys Asp Ser Asp Ser Gln   1 5 10       <210> 145 <211> 8 <212> PRT <213> Homo sapiens    <400> 145 Leu Gln Thr Asn Asn Ile Gln Gly   1 5       <210> 146 <211> 17 <212> PRT <213> Homo sapiens    <400> 146 Asn Lys Asn His Ser Glu Ser Thr Ile Val Lys Leu Cys Tyr Ile Asn   1 5 10 15 Phe       <210> 147 <211> 17 <212> PRT <213> Homo sapiens    <400> 147 Val Cys Asn Asn Leu Thr Ser Lys Cys Tyr Val Ile Thr Ile Asn Asn   1 5 10 15 Gly       <210> 148 <211> 28 <212> PRT <213> Homo sapiens    <400> 148 Arg Glu His Leu Trp Lys Phe Ser Asn Tyr Leu Ser Tyr Tyr Thr Val   1 5 10 15 Cys Arg Met Asn Val Glu Met Ile Leu Leu Ala Phe              20 25       <210> 149 <211> 11 <212> PRT <213> Homo sapiens    <400> 149 Met Phe Cys Gly Leu Asn Val Phe Leu Leu Lys   1 5 10       <210> 150 <211> 28 <212> PRT <213> Homo sapiens    <400> 150 Ser Phe Trp Tyr Leu Phe Lys Leu His Phe Leu Arg Ser Gly Asn Phe   1 5 10 15 Arg Ile Ile Phe Ala Leu Phe Gln Phe Cys Asp Phe              20 25       <210> 151 <211> 6 <212> PRT <213> Homo sapiens    <400> 151 Asn Glu Cys Leu Val Tyr   1 5       <210> 152 <211> 14 <212> PRT <213> Homo sapiens    <400> 152 Ala Ser Trp Ser Phe Leu Pro His Val Val Lys Ser Ser Glu   1 5 10       <210> 153 <211> 18 <212> PRT <213> Homo sapiens    <400> 153 Thr Val Asn Lys Leu Pro Lys Thr Cys Leu Glu Phe His Phe Glu Ala   1 5 10 15 Ile Cys       <210> 154 <211> 19 <212> PRT <213> Homo sapiens    <400> 154 Tyr Leu Lys Cys Ile His Ile Cys Ser Tyr Val Lys Asn Cys Ile Val   1 5 10 15 Leu Arg Met       <210> 155 <211> 47 <212> PRT <213> Homo sapiens    <400> 155 Ser Met Ser Thr Leu Val Val Asn Ile Ser Asp Val Lys Thr Leu Phe   1 5 10 15 Ile Thr Val Asp Phe Lys Asn Lys Lys Ser Leu Pro Lys Tyr Tyr Gln              20 25 30 Lys Pro Leu Ser Leu Pro Glu Leu Pro Ser Leu Gly Lys Asn Arg          35 40 45       <210> 156 <211> 8 <212> PRT <213> Homo sapiens    <400> 156 Ile Lys Gln Arg Leu Cys Pro Phe   1 5       <210> 157 <211> 11 <212> PRT <213> Homo sapiens    <400> 157 Tyr Gln Thr Pro Gln Ile Leu Ser His Ile Phe   1 5 10       <210> 158 <211> 17 <212> PRT <213> Homo sapiens    <400> 158 His Ile Val Tyr Arg Lys Phe Thr Gly Tyr Ala Met Ile Lys Thr Phe   1 5 10 15 Lys       <210> 159 <211> 10 <212> PRT <213> Homo sapiens    <400> 159 Ile Asp Ser Cys Lys Arg Lys Asp Asn Ile   1 5 10       <210> 160 <211> 27 <212> PRT <213> Homo sapiens    <400> 160 Val Ala Arg Gln Ser Lys Val Ser Val Ile Ser Gly Ser Leu Leu Ile   1 5 10 15 Ile Glu Gln Ser Phe Pro Tyr Arg Ile Leu Leu              20 25       <210> 161 <211> 24 <212> PRT <213> Homo sapiens    <400> 161 Ser Leu Ser Leu Val Val Ile Ala Pro Ala Ala Phe Phe Arg Arg Gln   1 5 10 15 Leu Gly Gln Gly Asp Leu Asn Gly              20       <210> 162 <211> 7 <212> PRT <213> Homo sapiens    <400> 162 Met Cys Cys Phe Ala Cys Leu   1 5       <210> 163 <211> 92 <212> PRT <213> Homo sapiens    <400> 163 Asn Ser Ala Gln Ser Leu Val Ser Leu Ser Leu Ser Leu Leu His Leu   1 5 10 15 Ser Leu Ser Leu Leu Leu His Gln Ser Leu Arg Leu Arg His Gln Asp              20 25 30 Ala Ser Phe Phe Pro Glu Ala Ser Phe Phe Phe Phe Leu Arg Trp Ser          35 40 45 Phe Ala Leu Leu Pro Arg Leu Ala Cys Ser Ala Ala Ile Leu Ala Asp      50 55 60 Cys Asn Phe His Leu Pro Cys Ser His Glu Ser Phe Ala Ser Ala Ser  65 70 75 80 Gly Leu Ala Gly Ile Thr Gly Thr Cys His His Ala                  85 90       <210> 164 <211> 78 <212> PRT <213> Homo sapiens    <400> 164 Leu Ile Phe Val Phe Leu Val Glu Thr Gly Phe His His Val Gly Gln   1 5 10 15 Ala Ser Leu Lys Leu Leu Thr Leu Ser Asp Leu Pro Ala Leu Ala Ser              20 25 30 Gln Ser Ala Gly Ile Thr Gly Met Ser His Arg Val Leu Pro Arg His          35 40 45 Ile Lys Phe Asp Arg Tyr Cys Ile Pro Phe Gly Ser Leu Gly Ile Asn      50 55 60 Phe Cys Leu Cys His Ser Ala Leu Tyr Ile Leu Lys Trp Arg  65 70 75       <210> 165 <211> 17 <212> PRT <213> Homo sapiens    <400> 165 Gly Gly Leu Gly Arg Lys Ile Ala Arg Ile Pro Lys Pro Cys Asn Thr   1 5 10 15 His       <210> 166 <211> 7 <212> PRT <213> Homo sapiens    <400> 166 Glu Phe Gln Ile His Tyr Ile   1 5       <210> 167 <211> 12 <212> PRT <213> Homo sapiens    <400> 167 Arg Ala Ser Glu Gly Asn Ser Ile Val Asn Trp Val   1 5 10       <210> 168 <211> 6 <212> PRT <213> Homo sapiens    <400> 168 Ser Val Arg Pro Lys Gly   1 5       <210> 169 <211> 5 <212> PRT <213> Homo sapiens    <400> 169 Asp Cys Thr Val Leu   1 5       <210> 170 <211> 5 <212> PRT <213> Homo sapiens    <400> 170 Thr Ser Ala Lys Val   1 5       <210> 171 <211> 57 <212> PRT <213> Homo sapiens    <400> 171 Met Leu Ser Val Ser Leu Val Phe Ile Ser Ala Ser Ser Ser Leu Leu   1 5 10 15 Gly Tyr Ile Val Val Leu Phe Pro Val Trp His Leu Ser Leu Val Phe              20 25 30 His Tyr Gly Lys Phe Ile Lys Lys Leu Ala Pro Leu Leu Ser Ser Ser          35 40 45 Asn Ala His Lys Glu Met Glu Asp Ile      50 55       <210> 172 <211> 7 <212> PRT <213> Homo sapiens    <400> 172 Ala Arg Glu Ile Thr Leu His   1 5       <210> 173 <211> 33 <212> PRT <213> Homo sapiens    <400> 173 Ile Ser Ser Phe Phe Leu Leu Asp Leu Asn Val Ser Ser His Ser Asn   1 5 10 15 Leu Trp Gly Leu Leu Val Phe Ser Tyr Cys Thr Leu Tyr Val Glu Leu              20 25 30 Phe       <210> 174 <211> 19 <212> PRT <213> Homo sapiens    <400> 174 Asn Ile Lys His Ile Tyr Phe Glu Phe Glu Leu Phe Leu Asn Phe Val   1 5 10 15 Phe Ile Leu       <210> 175 <211> 11 <212> PRT <213> Homo sapiens    <400> 175 Ile Lys Cys Lys Ser Lys Lys Lys Lys Lys Lys   1 5 10          <210> 176 <211> 5 <212> PRT <213> Homo sapiens    <400> 176 Gly Thr Pro Leu Lys   1 5       <210> 177 <211> 9 <212> PRT <213> Homo sapiens    <400> 177 Ala Cys Pro Ile Lys Thr Ser Val Ile   1 5       <210> 178 <211> 13 <212> PRT <213> Homo sapiens    <400> 178 Phe Phe Lys Lys Asp Thr Leu His Lys Glu Ser Phe Ile   1 5 10       <210> 179 <211> 39 <212> PRT <213> Homo sapiens    <400> 179 Lys Val Leu Ser Cys Ser Thr Phe Lys Val Leu Ile His Ser Cys Ile   1 5 10 15 Thr Glu Ser Ser Phe Glu Pro Phe Leu Gly Arg Glu Ala Cys Leu Ser              20 25 30 Ser Ser Val Trp Pro Ser Lys          35       <210> 180 <211> 12 <212> PRT <213> Homo sapiens    <400> 180 Leu Leu His Trp Asn Gln Phe Phe Ser Leu Leu Lys   1 5 10       <210> 181 <211> 8 <212> PRT <213> Homo sapiens    <400> 181 Ile Leu Cys His Lys Asn Lys Arg   1 5       <210> 182 <211> 12 <212> PRT <213> Homo sapiens    <400> 182 Arg Ala Lys Leu Met Leu Thr Ile Phe Ser Leu Leu   1 5 10       <210> 183 <211> 36 <212> PRT <213> Homo sapiens    <400> 183 Leu Cys Gln Gln Val Phe Ile Asn Thr Tyr Tyr Gly Lys Val Thr Val   1 5 10 15 Val Gly Ile Glu Asn Tyr Ile Ile Phe Lys Ala Val Phe Val Pro Arg              20 25 30 Trp Thr His His          35       <210> 184 <211> 10 <212> PRT <213> Homo sapiens    <400> 184 Gln Arg Leu Gly Ser Leu Glu Gly Ile Gly   1 5 10       <210> 185 <211> 34 <212> PRT <213> Homo sapiens    <400> 185 Glu Asn Gly Lys Met Glu Try Arg Arg Val Val Lys Val Leu Ser Val   1 5 10 15 Ser Asp Phe Val Tyr Leu Asn Asn Gly Pro Cys Leu Gly Ala Tyr Cys              20 25 30 Val Ser       <210> 186 <211> 11 <212> PRT <213> Homo sapiens    <400> 186 Glu Val Lys Gly Ile Cys Lys Val Ser Tyr Lys   1 5 10       <210> 187 <211> 13 <212> PRT <213> Homo sapiens    <400> 187 Pro Ile Asn Leu Leu Thr Thr Val Leu Asn Met Gln Arg   1 5 10       <210> 188 <211> 31 <212> PRT <213> Homo sapiens    <400> 188 Lys Pro Ser Ile Thr Ala Thr Gln Arg Glu Leu Val Leu Gly Asp Val   1 5 10 15 Gln Met Gly Leu Leu Val Lys Arg Ala Ile Thr Gly Phe Leu Ser              20 25 30       <210> 189 <211> 20 <212> PRT <213> Homo sapiens    <400> 189 Glu Val Val Thr Glu Met Arg Leu Phe Tyr Leu Phe Glu Tyr Arg Ser   1 5 10 15 Leu Val Leu Ser              20    <210> 190 <211> 19 <212> PRT <213> Homo sapiens    <400> 190 Arg Ser Phe Leu Phe Phe Cys Leu Phe Val Cys Phe Gly Ser Leu Val   1 5 10 15 Ile Leu Leu       <210> 191 <211> 32 <212> PRT <213> Homo sapiens    <400> 191 His Leu Phe Leu Leu Phe Phe Lys Glu Arg Lys Pro Thr Glu Met Phe   1 5 10 15 Ala Leu Thr Asn Ile Leu Ile Ser Ser Leu Gly Phe Phe Phe Pro Phe              20 25 30       <210> 192 <211> 6 <212> PRT <213> Homo sapiens    <400> 192 Leu Leu Tyr Ala Thr Thr   1 5       <210> 193 <211> 37 <212> PRT <213> Homo sapiens    <400> 193 Val Ile Phe Leu Lys Lys His Asn Val Ile Glu Ser Ile Ile Glu Lys   1 5 10 15 Asp His Ser His Ile Glu Phe Val Lys Ala Lys Glu Ile Glu Gly Ser              20 25 30 Asp Ile Phe Ile Leu          35       <210> 194 <211> 53 <212> PRT <213> Homo sapiens    <400> 194 Ile Leu Cys Thr Arg Ile Pro Gly Arg Val Phe Tyr Pro Trp Lys Gln   1 5 10 15 Val Ser Asp Tyr Phe Val Phe Thr Val Arg Val Ser Ser Leu Glu Met              20 25 30 Leu Thr Leu Lys Ser Val Phe Phe Ser Leu Tyr Leu Lys Ile Val Asn          35 40 45 Ile Leu Ile Ser Ser      50       <210> 195 <211> 40 <212> PRT <213> Homo sapiens    <400> 195 Leu Asp Glu Phe Lys His Ile Phe Arg Ser Val Thr Val Thr Ala Asn   1 5 10 15 Arg Thr Asp Asn Ile Ser Phe Lys Pro Ile Ile Ser Arg Val Lys Ile              20 25 30 Lys Ile Ile Val Lys Val Arg Leu          35 40       <210> 196 <211> 12 <212> PRT <213> Homo sapiens    <400> 196 Asn Tyr Ala Ile Leu Thr Phe Lys Ser Val Ile Thr   1 5 10       <210> 197 <211> 5 <212> PRT <213> Homo sapiens    <400> 197 His Gln Asn Val Met   1 5       <210> 198 <211> 22 <212> PRT <213> Homo sapiens    <400> 198 Ile Met Ala Ser Glu Asn Ile Phe Gly Asn Ser Gln Ile Thr Phe Leu   1 5 10 15 Thr Thr Leu Phe Ala Glu              20       <210> 199 <211> 7 <212> PRT <213> Homo sapiens    <400> 199 Leu Ser Glu Cys Ser Val Gly   1 5       <210> 200 <211> 17 <212> PRT <213> Homo sapiens    <400> 200 Met Cys Phe Cys Leu Asn Lys Ala Phe Gly Ile Cys Leu Asn Tyr Thr   1 5 10 15 Ser       <210> 201 <211> 21 <212> PRT <213> Homo sapiens    <400> 201 Glu Val Glu Ile Leu Gly Ser Ser Leu Leu Cys Phe Ser Phe Val Ile   1 5 10 15 Phe Glu Met Asn Val              20       <210> 202 <211> 21 <212> PRT <213> Homo sapiens    <400> 202 Phe Thr Glu Pro Val Gly His Phe Phe Leu Met Ser Leu Ser Pro Val   1 5 10 15 Ser Lys Pro Glu Leu              20       <210> 203 <211> 7 <212> PRT <213> Homo sapiens    <400> 203 Ile Asn Tyr Gln Lys Leu Ala   1 5       <210> 204 <211> 10 <212> PRT <213> Homo sapiens    <400> 204 Asn Phe Ile Leu Lys Gln Phe Ala Asn Ile   1 5 10       <210> 205 <211> 14 <212> PRT <213> Homo sapiens    <400> 205 Ser Val Tyr Thr Phe Val Val Met Leu Lys Ile Val Leu Tyr   1 5 10       <210> 206 <211> 7 <212> PRT <213> Homo sapiens    <400> 206 Glu Cys Asn Gln Cys Leu Leu   1 5       <210> 207 <211> 41 <212> PRT <213> Homo sapiens    <400> 207 Thr Phe Leu Met Ser Lys Leu Tyr Ser Leu Leu Leu Ile Leu Arg Ile   1 5 10 15 Arg Asn His Cys Leu Asn Ile Thr Lys Ser His Cys Leu Tyr Pro Asn              20 25 30 Phe Pro Val Trp Glu Arg Ile Val Arg          35 40       <210> 208 <211> 36 <212> PRT <213> Homo sapiens    <400> 208 Asn Lys Gly Ser Ala Leu Ser Asp Thr Lys Leu His Arg Tyr Phe Leu   1 5 10 15 Thr Ser Phe Lys Thr Phe Cys Asn Asn Ile Leu Phe Ile Gly Ser Leu              20 25 30 Gln Gly Met Gln          35       <210> 209 <211> 20 <212> PRT <213> Homo sapiens    <400> 209 Leu Lys Leu Leu Ser Glu Leu Ile Val Ala Lys Glu Arg Ile Ile Phe   1 5 10 15 Lys Val Ser Glu              20       <210> 210 <211> 7 <212> PRT <213> Homo sapiens    <400> 210 Gln Asp Asn Leu Lys Phe Leu   1 5       <210> 211 <211> 5 <212> PRT <213> Homo sapiens    <400> 211 Tyr Leu Ala Leu Cys   1 5       <210> 212 <211> 18 <212> PRT <213> Homo sapiens    <400> 212 Ser Lys Val Ser Leu Thr Glu Ser Phe Tyr Glu Gln Gln Ala Arg Val   1 5 10 15 Tyr Pro       <210> 213 <211> 9 <212> PRT <213> Homo sapiens    <400> 213 His Leu Leu Arg Phe Ser Gly Asp Ser   1 5       <210> 214 <211> 36 <212> PRT <213> Homo sapiens    <400> 214 Met Asp Arg Cys Ala Val Leu Pro Ala Cys Arg Ile Gln Pro Ser Leu   1 5 10 15 Trp Ser Leu Ser Leu Ser Pro Ser Ser Thr Ser Pro Ser Leu Phe Phe              20 25 30 Cys Thr Arg Ala          35       <210> 215 <211> 18 <212> PRT <213> Homo sapiens    <400> 215 Gly Cys Ala Thr Lys Met Arg His Phe Phe Gln Arg Leu Leu Phe Phe   1 5 10 15 Phe Phe       <210> 216 <211> 36 <212> PRT <213> Homo sapiens    <400> 216 Asp Gly Val Leu Leu Cys Cys Pro Gly Trp His Ala Val Leu Gln Ser   1 5 10 15 Trp Leu Thr Ala Thr Ser Thr Ser Arg Val His Thr Ser Leu Leu Pro              20 25 30 Gln Pro Leu Asp          35       <210> 217 <211> 11 <212> PRT <213> Homo sapiens    <400> 217 Leu Gly Leu Gln Ala Arg Ala Thr Met Pro Ser   1 5 10       <210> 218 <211> 14 <212> PRT <213> Homo sapiens    <400> 218 Arg Arg Gly Phe Thr Met Leu Ala Arg Leu Val Ser Asn Ser   1 5 10       <210> 219 <211> 15 <212> PRT <213> Homo sapiens    <400> 219 Val Ile Cys Pro Pro Trp Pro Pro Lys Val Leu Gly Leu Gln Ala   1 5 10 15       <210> 220 <211> 20 <212> PRT <213> Homo sapiens    <400> 220 Val Thr Val Ser Cys Pro Asp Ile Ser Asn Leu Thr Gly Ile Val Tyr   1 5 10 15 Pro Leu Asp Leu              20       <210> 221 <211> 13 <212> PRT <213> Homo sapiens    <400> 221 Glu Leu Ile Phe Ala Ser Val Thr Gln Leu Cys Ile Phe   1 5 10       <210> 222 <211> 40 <212> PRT <213> Homo sapiens    <400> 222 Asn Gly Asp Lys Tyr Arg Glu Val Leu Glu Gly Lys Leu Pro Glu Phe   1 5 10 15 Pro Asn His Val Thr Leu Ile Glu Asn Ser Arg Ser Ile Ile Ser Lys              20 25 30 Gly Gln Val Lys Glu Thr Val Leu          35 40       <210> 223 <211> 9 <212> PRT <213> Homo sapiens    <400> 223 Thr Gly Tyr Asn Ser Leu Val Leu Asn   1 5       <210> 224 <211> 5 <212> PRT <213> Homo sapiens    <400> 224 Tyr Ile Leu Asn Leu   1 5       <210> 225 <211> 7 <212> PRT <213> Homo sapiens    <400> 225 Asp Pro Lys Val Asp Lys Gln   1 5       <210> 226 <211> 19 <212> PRT <213> Homo sapiens    <400> 226 Phe Lys Ile Val Gln Tyr Ser Lys Arg Leu Gln Arg Ser Arg Cys Tyr   1 5 10 15 Gln Tyr His       <210> 227 <211> 9 <212> PRT <213> Homo sapiens    <400> 227 Phe Leu Phe Leu Pro Val Ala Pro Phe   1 5       <210> 228 <211> 53 <212> PRT <213> Homo sapiens    <400> 228 Val Thr Leu Leu Ser Ser Phe Gln Cys Gly Ile Cys His Trp Phe Phe   1 5 10 15 Thr Met Ala Ser Ser Leu Lys Ser Leu Leu His Cys Tyr Leu Gln Val              20 25 30 Met Pro Ile Arg Arg Trp Lys Ile Ser Glu Thr Ile Lys Ala Leu Ala          35 40 45 Ser Arg Gln Glu Lys      50       <210> 229 <211> 10 <212> PRT <213> Homo sapiens    <400> 229 Arg Cys Ile Lys Phe Gln Val Ser Phe Cys   1 5 10       <210> 230 <211> 20 <212> PRT <213> Homo sapiens    <400> 230 Met Cys Leu Ala Thr Leu Ile Tyr Gly Gly Phe Trp Phe Phe Pro Ile   1 5 10 15 Val Leu Cys Met              20       <210> 231 <211> 24 <212> PRT <213> Homo sapiens    <400> 231 Asn Cys Phe Glu Ile Ser Ser Ile Phe Thr Leu Asn Leu Asn Ser Phe   1 5 10 15 Leu Ile Leu Tyr Leu Ser Phe Glu              20       <210> 232 <211> 9 <212> PRT <213> Homo sapiens    <400> 232 Asn Val Asn Pro Lys Lys Lys Lys Lys   1 5       <210> 233 <211> 9 <212> PRT <213> Homo sapiens    <400> 233 Lys Arg His Cys Asn Glu Ala His His   1 5       <210> 234 <211> 9 <212> PRT <213> Homo sapiens    <400> 234 Ser Glu His Ala Gln Leu Lys Pro Val   1 5       <210> 235 <211> 31 <212> PRT <213> Homo sapiens    <400> 235 Tyr Arg Ile Arg Lys Ser Asp Phe Ser Lys Lys Ile Leu Tyr Ile Lys   1 5 10 15 Asn Pro Ser Tyr Lys Lys Phe Phe Leu Val Val His Leu Lys Phe              20 25 30       <210> 236 <211> 8 <212> PRT <213> Homo sapiens    <400> 236 Leu Arg Val Pro Leu Ser Pro Phe   1 5       <210> 237 <211> 25 <212> PRT <213> Homo sapiens    <400> 237 Ala Gly Arg His Val Cys His Leu Ala Cys Gly Pro Val Ser Asp Tyr   1 5 10 15 Tyr Ile Gly Ile Ser Phe Ser Val Phe              20 25       <210> 238 <211> 14 <212> PRT <213> Homo sapiens    <400> 238 Asn Lys Phe Tyr Ala Ile Arg Ile Lys Asp Lys Glu Gln Asn   1 5 10       <210> 239 <211> 46 <212> PRT <213> Homo sapiens    <400> 239 Leu Phe Leu Ala Tyr Tyr Asn Tyr Val Asn Lys Cys Leu Leu Ile Pro   1 5 10 15 Ile Met Gly Lys Ser Leu Trp Leu Ala Leu Lys Ile Thr Ser Ser Leu              20 25 30 Lys Gln Tyr Leu Ser Pro Asp Gly Leu Ile Thr Ser Lys Asp          35 40 45       <210> 240 <211> 5 <212> PRT <213> Homo sapiens    <400> 240 Val His Trp Lys Ala   1 5       <210> 241 <211> 17 <212> PRT <213> Homo sapiens    <400> 241 Gly Glu Arg Met Gly Arg Trp Ser Gly Gly Gly Leu Leu Lys Cys Cys   1 5 10 15 Gln       <210> 242 <211> 5 <212> PRT <213> Homo sapiens    <400> 242 Val Ile Leu Ser Thr   1 5       <210> 243 <211> 14 <212> PRT <213> Homo sapiens    <400> 243 Ile Met Val His Val Trp Gly His Ile Val Phe His Lys Lys   1 5 10       <210> 244 <211> 5 <212> PRT <213> Homo sapiens    <400> 244 Lys Val Phe Ala Lys   1 5       <210> 245 <211> 5 <212> PRT <213> Homo sapiens    <400> 245 Ala Thr Asn Asp Pro   1 5       <210> 246 <211> 45 <212> PRT <213> Homo sapiens    <400> 246 Gln Gln Ser Leu Ile Cys Lys Asp Glu Asn Gln Ala Leu Leu Leu Pro   1 5 10 15 Lys Gly Asn Trp Cys Leu Val Met Cys Arg Trp Gly Cys Trp Leu Arg              20 25 30 Glu Leu Leu Gln Val Phe Ser Leu Arg Phe His Arg Arg          35 40 45       <210> 247 <211> 12 <212> PRT <213> Homo sapiens    <400> 247 Asp Cys Phe Ile Phe Leu Asn Thr Asp Leu Leu Ser   1 5 10       <210> 248 <211> 23 <212> PRT <213> Homo sapiens    <400> 248 Val Ser Ser Glu Asp Gly Ser Asn Lys Gly Val Phe Cys Phe Phe Val   1 5 10 15 Cys Leu Phe Val Leu Ala Pro              20       <210> 249 <211> 21 <212> PRT <213> Homo sapiens    <400> 249 Tyr Ser Ser Asp Ile Tyr Phe Tyr Tyr Ser Ser Lys Lys Gly Asn Gln   1 5 10 15 Leu Lys Cys Leu Leu              20       <210> 250 <211> 31 <212> PRT <213> Homo sapiens    <400> 250 Val Leu Trp Val Phe Phe Ser Pro Phe Lys Lys Ile Ser Ile Tyr His   1 5 10 15 Ser Asn Lys Arg Thr Asn Val Asn Tyr Cys Met Leu Gln Leu Lys              20 25 30       <210> 251 <211> 19 <212> PRT <213> Homo sapiens    <400> 251 Arg Ser Thr Met Ser Leu Lys Val Leu Leu Lys Arg Ile Ile Val Thr   1 5 10 15 Leu Asn Leu       <210> 252 <211> 48 <212> PRT <213> Homo sapiens    <400> 252 Arg Pro Lys Lys Leu Lys Gly Val Ile Phe Ser Phe Tyr Asp Ile His   1 5 10 15 Ile Ser Lys Phe Cys Val Gln Glu Tyr Gln Ala Glu Cys Phe Thr His              20 25 30 Gly Asn Arg Phe Gln Ile Thr Leu Phe Leu Leu Leu Glu Ser Gln Val          35 40 45       <210> 253 <211> 10 <212> PRT <213> Homo sapiens    <400> 253 His Leu Asn Gln Phe Phe Ser His Tyr Thr   1 5 10       <210> 254 <211> 5 <212> PRT <213> Homo sapiens    <400> 254 Arg Leu Leu Ile Phe   1 5       <210> 255 <211> 14 <212> PRT <213> Homo sapiens    <400> 255 Tyr Leu Pro Ser Leu Met Asn Leu Asn Ile Ser Ser Asp Leu   1 5 10       <210> 256 <211> 12 <212> PRT <213> Homo sapiens    <400> 256 Gln Pro Ile Gly Leu Ile Ile Leu Ala Ser Asn Gln   1 5 10       <210> 257 <211> 5 <212> PRT <213> Homo sapiens    <400> 257 Tyr Pro Gly Leu Lys   1 5       <210> 258 <211> 9 <212> PRT <213> Homo sapiens    <400> 258 Lys Tyr Asp Cys Lys Ile Met Leu Tyr   1 5       <210> 259 <211> 11 <212> PRT <213> Homo sapiens    <400> 259 Leu Asp Ile Lys Met Leu Cys Asn Tyr His Lys   1 5 10       <210> 260 <211> 41 <212> PRT <213> Homo sapiens    <400> 260 Trp Leu Ala Arg Thr Ser Leu Glu Ile Leu Lys Leu Pro Phe Leu Leu   1 5 10 15 His Cys Leu Gln Asn Glu Cys Arg Asn Asp Pro Val Ser Phe Leu Asn              20 25 30 Val Leu Trp Val Glu Cys Val Phe Ala          35 40       <210> 261 <211> 7 <212> PRT <213> Homo sapiens    <400> 261 Ile Lys Leu Leu Val Phe Val   1 5       <210> 262 <211> 9 <212> PRT <213> Homo sapiens    <400> 262 Ile Thr Leu Leu Glu Lys Trp Lys Phe   1 5       <210> 263 <211> 9 <212> PRT <213> Homo sapiens    <400> 263 Asp His Leu Cys Phe Val Ser Val Leu   1 5       <210> 264 <211> 15 <212> PRT <213> Homo sapiens    <400> 264 Met Phe Ser Leu Leu Ser Gln Leu Val Ile Ser Ser Ser Cys Arg   1 5 10 15       <210> 265 <211> 6 <212> PRT <213> Homo sapiens    <400> 265 Val Ser Leu Asn Cys Glu   1 5       <210> 266 <211> 10 <212> PRT <213> Homo sapiens    <400> 266 Ile Thr Lys Asn Leu Leu Arg Ile Ser Phe   1 5 10       <210> 267 <211> 12 <212> PRT <213> Homo sapiens    <400> 267 Ser Asn Leu Leu Ile Phe Glu Val Tyr Thr His Leu   1 5 10       <210> 268 <211> 18 <212> PRT <213> Homo sapiens    <400> 268 Lys Leu Tyr Cys Thr Lys Asn Val Ile Asn Val Tyr Phe Ser Cys Lys   1 5 10 15 His Phe       <210> 269 <211> 8 <212> PRT <213> Homo sapiens    <400> 269 Cys Gln Asn Phe Ile His Tyr Cys   1 5    <210> 270 <211> 49 <212> PRT <213> Homo sapiens    <400> 270 Ile Leu Pro Lys Ala Thr Val Ser Thr Arg Thr Ser Gln Phe Gly Lys   1 5 10 15 Glu Ser Leu Asp Lys Thr Lys Ala Leu Pro Phe Leu Ile Pro Asn Ser              20 25 30 Thr Asp Thr Phe Ser His Leu Leu Lys His Phe Ala Ile Thr Tyr Cys          35 40 45 Leu       <210> 271 <211> 8 <212> PRT <213> Homo sapiens    <400> 271 Glu Val Tyr Arg Val Cys Asn Asp   1 5       <210> 272 <211> 5 <212> PRT <213> Homo sapiens    <400> 272 Leu Gln Lys Lys Gly   1 5       <210> 273 <211> 10 <212> PRT <213> Homo sapiens    <400> 273 Tyr Leu Arg Ser Val Ser Ser Lys Thr Ile   1 5 10       <210> 274 <211> 46 <212> PRT <213> Homo sapiens    <400> 274 Ser Phe Cys Asn Ile Trp Leu Ser Val Asn Tyr Arg Ala Lys Phe Pro   1 5 10 15 Leu Gln Asn Pro Phe Met Asn Ser Lys Leu Glu Ser Ile Pro Ser Gly              20 25 30 Tyr Ser Thr Cys Cys Val Phe Gln Glu Thr Val Arg Pro Gly          35 40 45       <210> 275 <211> 75 <212> PRT <213> Homo sapiens    <400> 275 Phe Glu Trp Ile Asp Val Leu Phe Cys Leu Leu Val Glu Phe Ser Pro   1 5 10 15 Val Phe Gly Leu Ser Leu Ser Leu Pro Pro Pro Pro Leu Pro Leu Ser              20 25 30 Ser Ser Ala Pro Glu Pro Lys Ala Ala Pro Pro Arg Cys Val Ile Phe          35 40 45 Ser Arg Gly Phe Phe Phe Phe Phe Phe Glu Met Glu Phe Cys Ser Val      50 55 60 Ala Gln Ala Gly Met Gln Cys Cys Asn Leu Gly  65 70 75       <210> 276 <211> 46 <212> PRT <213> Homo sapiens    <400> 276 Leu Gln Leu Pro Pro Val Phe Thr Arg Val Phe Cys Leu Ser Leu   1 5 10 15 Trp Ile Ser Trp Asp Tyr Arg His Val Pro Pro Cys Leu Ala Asn Phe              20 25 30 Cys Val Phe Ser Arg Asp Gly Val Ser Pro Cys Trp Pro Gly          35 40 45       <210> 277 <211> 7 <212> PRT <213> Homo sapiens    <400> 277 Ser Gln Thr Pro Asp Leu Lys   1 5       <210> 278 <211> 25 <212> PRT <213> Homo sapiens    <400> 278 Ser Ala Arg Leu Gly Leu Pro Lys Cys Trp Asp Tyr Arg His Glu Ser   1 5 10 15 Pro Cys Pro Ala Gln Thr Tyr Gln Ile              20 25       <210> 279 <211> 11 <212> PRT <213> Homo sapiens    <400> 279 Gln Val Leu Tyr Thr Leu Trp Ile Phe Arg Asn   1 5 10       <210> 280 <211> 31 <212> PRT <213> Homo sapiens    <400> 280 Phe Leu Pro Leu Ser Leu Ser Phe Val Tyr Phe Glu Met Glu Ile Ser   1 5 10 15 Ile Gly Arg Ser Trp Lys Glu Asn Cys Gln Asn Ser Gln Thr Met              20 25 30       <210> 281 <211> 14 <212> PRT <213> Homo sapiens    <400> 281 His Ser Leu Arg Ile Pro Asp Pro Leu Tyr Leu Lys Gly Lys   1 5 10       <210> 282 <211> 55 <212> PRT <213> Homo sapiens    <400> 282 Arg Lys Gln Tyr Cys Glu Leu Gly Ile Thr Pro Trp Phe Leu Thr Ser   1 5 10 15 Thr Phe Leu Ile Cys Glu Thr Gln Arg Leu Ile Asn Asn Asn Leu Arg              20 25 30 Leu Tyr Ser Thr Leu Asn Val Cys Lys Gly Leu Asp Val Ile Ser Ile          35 40 45 Thr Ser Phe Tyr Phe Cys Gln      50 55       <210> 283 <211> 25 <212> PRT <213> Homo sapiens    <400> 283 Leu Pro Phe Arg Leu His Cys Cys Pro Leu Ser Ser Val Ala Ser Val   1 5 10 15 Ile Gly Phe Ser Leu Trp Gln Val His              20 25       <210> 284 <211> 9 <212> PRT <213> Homo sapiens    <400> 284 Lys Ala Cys Ser Ile Val Ile Phe Lys   1 5       <210> 285 <211> 11 <212> PRT <213> Homo sapiens    <400> 285 Gly Asp Gly Arg Tyr Leu Arg Gln Leu Arg Leu   1 5 10       <210> 286 <211> 22 <212> PRT <213> Homo sapiens    <400> 286 Leu Leu Gly Lys Arg Asn Asn Val Ala Leu Asn Phe Lys Phe Leu Ser   1 5 10 15 Ala Arg Leu Glu Cys Val              20       <210> 287 <211> 25 <212> PRT <213> Homo sapiens    <400> 287 Phe Met Gly Ala Phe Gly Phe Phe Leu Leu Tyr Phe Val Cys Arg Ile   1 5 10 15 Val Leu Lys Tyr Gln Ala Tyr Leu Leu              20 25       <210> 288 <211> 9 <212> PRT <213> Homo sapiens    <400> 288 Phe Cys Ile Tyr Pro Leu Asn Lys Met   1 5       <210> 289 <211> 7 <212> PRT <213> Homo sapiens    <400> 289 Ile Gln Lys Lys Lys Lys Lys   1 5       <210> 290 <211> 7 <212> PRT <213> Homo sapiens    <400> 290 Leu Ile Cys Glu Val Ser His   1 5       <210> 291 <211> 10 <212> PRT <213> Homo sapiens    <400> 291 Ser Leu Ser Pro Ser Val Cys Val Phe Leu   1 5 10       <210> 292 <211> 11 <212> PRT <213> Homo sapiens    <400> 292 Ser Thr Cys Val His Thr His Thr Gln Ile Tyr   1 5 10       <210> 293 <211> 67 <212> PRT <213> Homo sapiens    <400> 293 Ile Ser Lys Thr Lys Ile Lys Asn Lys Glu Val Ile Phe Ser Lys Gln   1 5 10 15 Thr Trp Ile Pro Ser Gln Ser Ala Gly Ile Thr Gly Met Ser His Arg              20 25 30 Val Leu Pro Arg His Ile Lys Phe Asp Arg Tyr Cys Ile Pro Phe Gly          35 40 45 Ser Leu Gly Ile Asn Phe Cys Leu Cys His Ser Ala Leu Tyr Ile Leu      50 55 60 Lys Trp Arg  65       <210> 294 <211> 17 <212> PRT <213> Homo sapiens    <400> 294 Gly Gly Leu Gly Arg Lys Ile Ala Arg Ile Pro Lys Pro Cys Asn Thr   1 5 10 15 His       <210> 295 <211> 7 <212> PRT <213> Homo sapiens    <400> 295 Glu Phe Gln Ile His Tyr Ile   1 5       <210> 296 <211> 12 <212> PRT <213> Homo sapiens    <400> 296 Arg Ala Ser Glu Gly Asn Ser Ile Val Asn Trp Val   1 5 10       <210> 297 <211> 6 <212> PRT <213> Homo sapiens    <400> 297 Ser Val Arg Pro Lys Gly   1 5       <210> 298 <211> 17 <212> PRT <213> Homo sapiens    <400> 298 Asp Cys Gln Tyr Ser Lys Arg Leu Gln Arg Ser Arg Cys Tyr Gln Tyr   1 5 10 15 His       <210> 299 <211> 9 <212> PRT <213> Homo sapiens    <400> 299 Phe Leu Phe Leu Pro Val Ala Pro Phe   1 5       <210> 300 <211> 53 <212> PRT <213> Homo sapiens    <400> 300 Val Thr Leu Leu Ser Ser Phe Gln Cys Gly Ile Cys His Trp Phe Phe   1 5 10 15 Thr Met Ala Ser Ser Leu Lys Ser Leu Leu His Cys Tyr Leu Gln Val              20 25 30 Met Pro Ile Arg Arg Trp Lys Ile Ser Glu Thr Ile Lys Ala Leu Ala          35 40 45 Ser Arg Gln Glu Lys      50       <210> 301 <211> 10 <212> PRT <213> Homo sapiens    <400> 301 Arg Cys Ile Lys Phe Gln Val Ser Phe Cys   1 5 10       <210> 302 <211> 20 <212> PRT <213> Homo sapiens    <400> 302 Met Cys Leu Ala Thr Leu Ile Tyr Gly Gly Phe Trp Phe Phe Pro Ile   1 5 10 15 Val Leu Cys Met              20       <210> 303 <211> 24 <212> PRT <213> Homo sapiens    <400> 303 Asn Cys Phe Glu Ile Ser Ser Ile Phe Thr Leu Asn Leu Asn Ser Phe   1 5 10 15 Leu Ile Leu Tyr Leu Ser Phe Glu              20       <210> 304 <211> 12 <212> PRT <213> Homo sapiens    <400> 304 Asn Val Asn Pro Lys Lys Lys Lys Lys Lys Lys Lys   1 5 10       <210> 305 <211> 34 <212> PRT <213> Homo sapiens    <400> 305 Tyr Val Lys Ser Val Ile Ser Leu His Asn Leu Cys Leu Pro Leu Cys   1 5 10 15 Val Ser Phe Tyr Lys Ala His Val Tyr Thr His Thr His Lys Tyr Thr              20 25 30 Glu Ser       <210> 306 <211> 12 <212> PRT <213> Homo sapiens    <400> 306 Thr Glu Tyr Gln Lys Pro Lys Ser Arg Thr Lys Lys   1 5 10       <210> 307 <211> 17 <212> PRT <213> Homo sapiens    <400> 307 Tyr Phe Pro Asn Lys His Gly Phe Pro Pro Lys Val Leu Gly Leu Gln   1 5 10 15 Ala       <210> 308 <211> 20 <212> PRT <213> Homo sapiens    <400> 308 Val Thr Val Ser Cys Pro Asp Ile Ser Asn Leu Thr Gly Ile Val Tyr   1 5 10 15 Pro Leu Asp Leu              20       <210> 309 <211> 13 <212> PRT <213> Homo sapiens    <400> 309 Glu Leu Ile Phe Ala Ser Val Thr Gln Leu Cys Ile Phe   1 5 10       <210> 310 <211> 40 <212> PRT <213> Homo sapiens    <400> 310 Asn Gly Asp Lys Tyr Arg Glu Val Leu Glu Gly Lys Leu Pro Glu Phe   1 5 10 15 Pro Asn His Val Thr Leu Ile Glu Asn Ser Arg Ser Ile Ile Ser Lys              20 25 30 Gly Gln Val Lys Glu Thr Val Leu          35 40       <210> 311 <211> 9 <212> PRT <213> Homo sapiens    <400> 311 Thr Gly Tyr Asn Ser Leu Val Leu Asn   1 5       <210> 312 <211> 5 <212> PRT <213> Homo sapiens    <400> 312 Tyr Ile Leu Asn Leu   1 5       <210> 313 <211> 7 <212> PRT <213> Homo sapiens    <400> 313 Asp Pro Lys Val Asp Lys Gln   1 5       <210> 314 <211> 25 <212> PRT <213> Homo sapiens    <400> 314 Phe Lys Ile Val Ser Thr Leu Asn Val Cys Lys Gly Leu Asp Val Ile   1 5 10 15 Ser Ile Thr Ser Phe Tyr Phe Cys Gln              20 25       <210> 315 <211> 25 <212> PRT <213> Homo sapiens    <400> 315 Leu Pro Phe Arg Leu His Cys Cys Pro Leu Ser Ser Val Ala Ser Val   1 5 10 15 Ile Gly Phe Ser Leu Trp Gln Val His              20 25       <210> 316 <211> 9 <212> PRT <213> Homo sapiens    <400> 316 Lys Ala Cys Ser Ile Val Ile Phe Lys   1 5       <210> 317 <211> 11 <212> PRT <213> Homo sapiens    <400> 317 Gly Asp Gly Arg Tyr Leu Arg Gln Leu Arg Leu   1 5 10       <210> 318 <211> 22 <212> PRT <213> Homo sapiens    <400> 318 Leu Leu Gly Lys Arg Asn Asn Val Ala Leu Asn Phe Lys Phe Leu Ser   1 5 10 15 Ala Arg Leu Glu Cys Val              20       <210> 319 <211> 25 <212> PRT <213> Homo sapiens    <400> 319 Phe Met Gly Ala Phe Gly Phe Phe Leu Leu Tyr Phe Val Cys Arg Ile   1 5 10 15 Val Leu Lys Tyr Gln Ala Tyr Leu Leu              20 25       <210> 320 <211> 9 <212> PRT <213> Homo sapiens    <400> 320 Phe Cys Ile Tyr Pro Leu Asn Lys Met   1 5       <210> 321 <211> 9 <212> PRT <213> Homo sapiens    <400> 321 Ile Gln Lys Lys Lys Lys Lys Lys Lys   1 5       <210> 322 <211> 78 <212> PRT <213> Homo sapiens    <400> 322 Ser Gln Ser Leu Val Cys Ile Ile Ser Val Ser Leu Cys Val Cys Leu   1 5 10 15 Ser Ile Lys His Met Cys Thr His Thr His Thr Asn Ile Leu Lys Ala              20 25 30 Arg Val Ser Ser Lys Leu Asn Ile Lys Asn Gln Asn Gln Glu Gln Arg          35 40 45 Ser Asp Ile Phe Gln Thr Asn Met Asp Ser Leu Pro Lys Cys Trp Asp      50 55 60 Tyr Arg His Glu Ser Pro Cys Pro Ala Gln Thr Tyr Gln Ile  65 70 75       <210> 323 <211> 11 <212> PRT <213> Homo sapiens    <400> 323 Gln Val Leu Tyr Thr Leu Trp Ile Phe Arg Asn   1 5 10       <210> 324 <211> 31 <212> PRT <213> Homo sapiens    <400> 324 Phe Leu Pro Leu Ser Leu Ser Phe Val Tyr Phe Glu Met Glu Ile Ser   1 5 10 15 Ile Gly Arg Ser Trp Lys Glu Asn Cys Gln Asn Ser Gln Thr Met              20 25 30       <210> 325 <211> 14 <212> PRT <213> Homo sapiens    <400> 325 His Ser Leu Arg Ile Pro Asp Pro Leu Tyr Leu Lys Gly Lys   1 5 10       <210> 326 <211> 36 <212> PRT <213> Homo sapiens    <400> 326 Arg Lys Gln Tyr Cys Glu Leu Gly Ile Thr Pro Trp Phe Leu Thr Ser   1 5 10 15 Thr Phe Leu Ile Cys Glu Thr Gln Arg Leu Ile Asn Asn Asn Leu Arg              20 25 30 Leu Ser Val Leu          35       <210> 327 <211> 5 <212> PRT <213> Homo sapiens    <400> 327 Thr Ser Ala Lys Val   1 5       <210> 328 <211> 57 <212> PRT <213> Homo sapiens    <400> 328 Met Leu Ser Val Ser Leu Val Phe Ile Ser Ala Ser Ser Ser Leu Leu   1 5 10 15 Gly Tyr Ile Val Val Leu Phe Pro Val Trp His Leu Ser Leu Val Phe              20 25 30 His Tyr Gly Lys Phe Ile Lys Lys Leu Ala Pro Leu Leu Ser Ser Ser          35 40 45 Asn Ala His Lys Glu Met Glu Asp Ile      50 55       <210> 329 <211> 7 <212> PRT <213> Homo sapiens    <400> 329 Ala Arg Glu Ile Thr Leu His   1 5       <210> 330 <211> 33 <212> PRT <213> Homo sapiens    <400> 330 Ile Ser Ser Phe Phe Leu Leu Asp Leu Asn Val Ser Ser His Ser Asn   1 5 10 15 Leu Trp Gly Leu Leu Val Phe Ser Tyr Cys Thr Leu Tyr Val Glu Leu              20 25 30 Phe       <210> 331 <211> 19 <212> PRT <213> Homo sapiens    <400> 331 Asn Ile Lys His Ile Tyr Phe Glu Phe Glu Leu Phe Leu Asn Phe Val   1 5 10 15 Phe Ile Leu       <210> 332 <211> 13 <212> PRT <213> Homo sapiens    <400> 332 Ile Lys Cys Lys Ser Lys Lys Lys Lys Lys Lys Lys Lys   1 5 10       <210> 333 <211> 63 <212> PRT <213> Homo sapiens    <400> 333 Lys Lys Ser Cys Leu Leu Phe Val Leu Gly Trp Ser Cys Arg Gly His   1 5 10 15 Gly Pro Ser His His Lys Trp Pro Arg Ala Cys Cys Gly Arg Glu Ala              20 25 30 Ser Pro Val Gly Pro Gly His Leu Thr Ser Ala Cys His Ser Gly Ser          35 40 45 Trp Ala Leu Leu Pro Pro Glu Cys Ser Cys Asn Ala Pro Phe Ala      50 55 60       <210> 334 <211> 49 <212> PRT <213> Homo sapiens    <400> 334 Ser Ser Arg Pro Cys Arg Gln Gly Pro Glu His Leu Phe Leu Pro Ser   1 5 10 15 Leu Ala Ser Glu Val Leu Arg Gly Asn Ser Pro Thr Leu Pro Pro Gln              20 25 30 Ser Ala Val Thr Gly Glu Ser Leu Gly Pro Gln Gln Gly Arg Pro Gly          35 40 45 Gly       <210> 335 <211> 32 <212> PRT <213> Homo sapiens    <400> 335 Asp Leu Gly Gly Ser Trp Pro Arg Ser Gly Arg Pro Val Trp Ser Gly   1 5 10 15 Leu His Leu Asn Arg Pro Arg Thr Gly Asp Leu Pro Arg Ala Gly Cys              20 25 30       <210> 336 <211> 17 <212> PRT <213> Homo sapiens    <400> 336 Cys Pro His Arg Ala Pro Arg Arg Cys Leu Leu Pro Gly Ala Thr Leu   1 5 10 15 Arg       <210> 337 <211> 27 <212> PRT <213> Homo sapiens    <400> 337 Thr Ala Ala Gly Gln Pro Val Pro Gly Glu His Arg Gln Lys His Cys   1 5 10 15 Arg Arg His His Arg Gly Gly Leu His Arg His              20 25       <210> 338 <211> 16 <212> PRT <213> Homo sapiens    <400> 338 Pro Gly His Ala Gly Gly Cys Pro Gly Ala Arg His Thr Gly His Pro   1 5 10 15       <210> 339 <211> 81 <212> PRT <213> Homo sapiens    <400> 339 Gly Ala Ala Val Gln Cys Arg Cys Pro Leu Val Arg Gly Arg Val Ser   1 5 10 15 Ala Ala Ala Ala Ala Gly Asp Ala Arg Glu Gln Ala Glu Gly Ser Gly              20 25 30 Gln Gly Pro Gly Pro His Ser Leu Pro Ala His Asp His Arg Gly Val          35 40 45 Arg Cys Arg Ser Arg Thr Val Gly His Pro Gly Gly Pro Arg Gly Gly      50 55 60 Gln Pro Leu Pro Ala Leu His Arg Gln Pro Gln Ala Thr Ser Gly Val  65 70 75 80 His       <210> 340 <211> 29 <212> PRT <213> Homo sapiens    <400> 340 Pro Ala Pro Leu Leu Pro Ala Trp Glu Gly Val Gln His Gln Pro Leu   1 5 10 15 Pro Ala Gly Gly Glu Ser Leu Gly Leu Gln Arg Asp Gln              20 25       <210> 341 <211> 37 <212> PRT <213> Homo sapiens    <400> 341 Pro His Gln Val Leu Ser Gln Gln Ala His Leu Arg Gly Gly Ile Trp   1 5 10 15 Ala Val Trp Ile His Pro Arg Ala His Arg Leu Pro Ser Glu His Pro              20 25 30 Asp Tyr Ser His Arg          35       <210> 342 <211> 181 <212> PRT <213> Homo sapiens    <400> 342 Gln His Arg Leu Gly Pro Glu Arg His Gly Leu Gln Leu Arg Arg Leu   1 5 10 15 Ser Gln His Leu Pro Arg His Val Gln Gly Ala Gly Gly Gly Ala Ala              20 25 30 Gln Arg Gln Leu His Gly Leu Cys His Ala Gln Gly Pro Arg Leu Pro          35 40 45 Leu Arg His Gln Arg Pro Ala Gln Gly Asp Thr Arg Val Ala His His      50 55 60 Gly Arg Gln Asp Leu Leu His Leu Leu Leu Arg Gly Arg Glu Gln Gln  65 70 75 80 Trp His Ile Arg Gly Gly Arg Pro Asp Pro Arg Gly His Leu Leu His                  85 90 95 Leu Gly Cys Pro Thr Pro Thr Pro Pro Ser Leu Arg Gly Asp Ser Arg             100 105 110 Ala Pro Gly His His Leu Leu Leu Gly Pro Pro His His Ala Val Pro         115 120 125 Gly Pro Val Ser Pro Arg Pro Ser Val His Ser Met Pro Pro Phe Ser     130 135 140 Ala Ser Gly Arg Gly Cys Pro Val Phe Thr Thr Ser Val Ala Ala Gly 145 150 155 160 Ser Gly Gln Pro Gly Arg Trp Pro Gly Gln Trp Pro Gly Pro Val Glu                 165 170 175 Thr Ile Pro Gln Asp             180       <210> 343 <211> 102 <212> PRT <213> Homo sapiens    <400> 343 Gly Gln Gly Cys Ala Gly Leu Gly Gln Gly Pro Arg Thr Arg Ser Ser   1 5 10 15 Gly Arg Leu Pro Thr Ser Ser Ala Gly Gly Ala Pro Arg Ala Ser Leu              20 25 30 Ala Ser Leu His Cys Thr Leu Gln Cys Ile Cys Asp Ser His Phe Ser          35 40 45 Ala Arg Ser Gln Pro Gly Trp Arg Cys Ser Gln Ser Arg Gly Ser Gln      50 55 60 Thr Leu Arg Ser Phe Cys Ser Cys Pro Phe Ile Arg Thr Arg Ala Pro  65 70 75 80 Pro Val Thr Cys Pro Arg Pro Pro Lys Pro Ser Leu Arg Gly Val Pro                  85 90 95 Thr Ala Trp Met Pro Ala             100       <210> 344 <211> 165 <212> PRT <213> Homo sapiens    <400> 344 Val Leu Arg Thr Gln Asp Ser Val Trp Gly Arg Pro Leu Pro Asp Arg   1 5 10 15 Pro Ser Pro Gly Pro Gly Gly Glu Arg Phe Ala Val Ser Val Leu Ile              20 25 30 His Leu Met Gly Pro Asp Lys Gly Pro Arg Cys Pro Ala Ser Leu Asp          35 40 45 Gly Pro Arg Gly Pro Cys Ser Pro Arg Trp Asp Ser Asp Pro Val Pro      50 55 60 Gln Ser Ser Pro Ala Ala Glu Trp Gly Pro Ser Arg Pro Arg Pro Gly  65 70 75 80 Pro Gly Ala Leu Leu Ala Cys Thr Tyr Cys Cys Pro Ser Pro Pro Gly                  85 90 95 Ala Val Gly Ala Thr Pro Arg Cys Trp Gly His Lys Pro Leu Pro Thr             100 105 110 Pro Gly His Gly Pro His Pro Pro Arg Val Phe Leu Pro Cys Asp Ser         115 120 125 Trp Asn Leu Arg Pro Pro Gln Ser His Gly Arg Gly Val Leu Leu Arg     130 135 140 Pro Cys Pro Gln Met Ile Phe Leu Asn Lys Glu Thr Asn Ala Pro Ala 145 150 155 160 Lys Lys Lys Lys Lys                 165       <210> 345 <211> 85 <212> PRT <213> Homo sapiens    <400> 345 Arg Ser His Val Cys Cys Leu Ser Trp Asp Gly Ala Ala Gly Asp Thr   1 5 10 15 Ala Pro Pro Thr Thr Ser Gly Gln Gly His Val Val Val Gly Lys Leu              20 25 30 His Arg Ser Ala Pro Ala Thr Ser Pro Leu Pro Ala Thr Arg Gly Pro          35 40 45 Gly Pro Cys Cys Pro Pro Ser Ala Ala Ala Thr Pro Leu Leu Pro Lys      50 55 60 Ala Ala Gly Pro Ala Asp Arg Asp Leu Ser Ile Phe Phe Phe Leu Pro  65 70 75 80 Trp Pro Leu Arg Ser                  85       <210> 346 <211> 46 <212> PRT <213> Homo sapiens    <400> 346 Glu Gly Thr Pro Gln Leu Ser Arg Pro Ser Gln Arg Ser Gln Gly Ser   1 5 10 15 Leu Trp Ala His Asn Arg Ala Gly Leu Val Ala Glu Thr Leu Val Ala              20 25 30 Pro Gly His Ala Gln Glu Gly Pro Cys Gly Gln Gly Cys Ile          35 40 45       <210> 347 <211> 323 <212> PRT <213> Homo sapiens    <400> 347 Thr Gly Pro Ala Leu Gly Ile Cys Arg Gly Leu Gly Ala Asp Val Pro   1 5 10 15 Thr Ala Pro Pro Val Asp Val Ser Cys Gln Ala Arg Leu Phe Asp Glu              20 25 30 Pro Gln Leu Ala Ser Leu Cys Leu Glu Asn Ile Asp Lys Asn Thr Ala          35 40 45 Asp Ala Ile Thr Ala Glu Gly Phe Thr Asp Ile Asp Leu Asp Thr Leu      50 55 60 Val Ala Val Leu Glu Arg Asp Thr Leu Gly Ile Arg Glu Val Arg Leu  65 70 75 80 Phe Asn Ala Val Val Arg Trp Ser Glu Ala Glu Cys Gln Arg Gln Gln                  85 90 95 Leu Gln Val Thr Pro Glu Asn Arg Arg Lys Val Leu Gly Lys Ala Leu             100 105 110 Gly Leu Ile Arg Phe Pro Leu Met Thr Ile Glu Glu Phe Ala Ala Gly         115 120 125 Pro Ala Gln Ser Gly Ile Leu Val Asp Arg Glu Val Val Ser Leu Phe     130 135 140 Leu His Phe Thr Val Asn Pro Lys Pro Arg Val Glu Phe Ile Asp Arg 145 150 155 160 Pro Arg Cys Cys Leu Arg Gly Lys Glu Cys Ser Ile Asn Arg Phe Gln                 165 170 175 Gln Val Glu Ser Arg Trp Gly Tyr Ser Gly Thr Ser Asp Arg Ile Arg             180 185 190 Phe Ser Val Asn Lys Arg Ile Phe Val Val Gly Phe Gly Leu Tyr Gly         195 200 205 Ser Ile His Gly Pro Thr Asp Tyr Gln Val Asn Ile Gln Ile Ile His     210 215 220 Thr Asp Ser Asn Thr Val Leu Gly Gln Asn Asp Thr Gly Phe Ser Cys 225 230 235 240 Asp Gly Ser Ala Ser Thr Phe Arg Val Met Phe Lys Glu Pro Val Glu                 245 250 255 Val Leu Pro Asn Val Asn Tyr Thr Ala Cys Ala Thr Leu Lys Gly Pro             260 265 270 Asp Ser His Tyr Gly Thr Lys Gly Leu Arg Lys Val Thr His Glu Ser         275 280 285 Pro Thr Thr Gly Ala Lys Thr Cys Phe Thr Phe Cys Tyr Ala Ala Gly     290 295 300 Asn Asn Asn Gly Thr Ser Val Glu Asp Gly Gln Ile Pro Glu Val Ile 305 310 315 320 Phe Tyr Thr       <210> 348 <211> 221 <212> PRT <213> Homo sapiens    <400> 348 Ala Ala Arg His Arg His Arg Pro Pro Ser Val Gly Ile Ala Glu Pro   1 5 10 15 Gln Ala Ile Ile Cys Cys Trp Gly Pro Pro Thr Thr Arg Cys Gln Ala              20 25 30 Gln Cys Pro Pro Gly Arg Leu Ser Thr Pro Cys His Leu Ser Gln His          35 40 45 Gln Asp Gly Val Ala Leu Cys Ser Pro Arg Val Trp Leu Leu Asp Gln      50 55 60 Gly Ser Arg Gly Gly Gly Gln Ala Ser Gly Gln Ala Leu Trp Arg Gln  65 70 75 80 Ser Leu Arg Thr Arg Asp Arg Ala Val Pro Ala Trp Ala Arg Ala His                  85 90 95 Gly Pro Ala Ala Gln Gly Ala Cys Pro Arg Arg Leu Pro Ala Val Arg             100 105 110 Arg Gly Arg Pro Ser Arg Leu Phe Thr Ala His Cys Asn Ala Phe Ala         115 120 125 Ile Pro Ile Ser Leu Leu Gly Ala Ser Leu Gly Gly Ala Ala Pro Arg     130 135 140 Ala Val Gly Pro Arg Pro Cys Val Pro Phe Val Pro Val Arg Leu Ser 145 150 155 160 Gly His Gly Pro His Leu Ser Arg Ala Arg Gly His Pro Ser Pro Ala                 165 170 175 Cys Gly Ala Phe Pro Leu Pro Gly Cys Arg Leu Glu Phe Cys Ala Arg             180 185 190 Arg Ile Gln Cys Gly Asp Gly Pro Cys Arg Ile Gly Leu Ala Leu Ala         195 200 205 Gln Val Val Ser Gly Leu Gln Cys Pro Phe Ser Ser Thr     210 215 220       <210> 349 <211> 114 <212> PRT <213> Homo sapiens    <400> 349 Trp Ala Gln Ile Lys Ala Pro Ala Val Gln Pro Pro Trp Thr Ala Leu   1 5 10 15 Ala Val Pro Ala Ala Gln Asp Gly Thr Gln Thr Leu Cys Pro Arg Ala              20 25 30 Pro Leu Pro Gln Asn Gly Ala Pro Ala Gly Pro Asp Arg Val Gln Glu          35 40 45 His Cys Ser Pro Val His Thr Val Ala Leu Ala His Leu Val Pro Trp      50 55 60 Glu Pro Pro Pro Gly Ala Gly Gly Thr Ser Pro Ser Pro Leu Arg Ala  65 70 75 80 Thr Ala Pro Thr His Pro Ala Cys Phe Cys Pro Val Thr Pro Gly Thr                  85 90 95 Cys Val Leu Pro Lys Ala Met Gly Gly Val Ser Ser Ser Asp His Ala             100 105 110 Pro Arg       <210> 350 <211> 13 <212> PRT <213> Homo sapiens    <400> 350 Ile Lys Lys Gln Met His Leu Gln Lys Lys Lys Lys Lys   1 5 10       <210> 351 <211> 72 <212> PRT <213> Homo sapiens    <400> 351 Glu Val Met Ser Ala Val Cys Leu Gly Met Glu Leu Pro Gly Thr Arg   1 5 10 15 Pro Leu Pro Pro Gln Val Ala Lys Gly Met Leu Trp Ser Gly Ser Phe              20 25 30 Thr Gly Arg Pro Arg Pro Pro His Leu Cys Leu Pro Leu Gly Val Leu          35 40 45 Gly Pro Ala Ala Pro Arg Val Gln Leu Gln Arg Pro Phe Cys Leu Lys      50 55 60 Gln Gln Ala Leu Pro Thr Gly Thr  65 70       <210> 352 <211> 9 <212> PRT <213> Homo sapiens    <400> 352 Ala Ser Phe Ser Ser Phe Leu Gly Leu   1 5       <210> 353 <211> 148 <212> PRT <213> Homo sapiens    <400> 353 Gly Pro Glu Arg Glu Leu Pro Asn Ser Pro Ala Pro Val Ser Gly His   1 5 10 15 Arg Gly Val Ser Gly Pro Thr Thr Gly Pro Ala Trp Trp Leu Arg Pro              20 25 30 Trp Trp Leu Leu Ala Thr Leu Arg Lys Ala Arg Val Val Arg Ala Ala          35 40 45 Phe Glu Pro Ala Pro His Trp Gly Ser Ala Glu Gly Trp Val Leu Met      50 55 60 Ser Pro Pro Arg Pro Pro Ser Met Ser Leu Ala Arg Arg Asp Ser Ser  65 70 75 80 Met Asn Arg Ser Trp Pro Ala Cys Ala Trp Arg Thr Ser Thr Lys Thr                  85 90 95 Leu Gln Thr Pro Ser Pro Arg Arg Ala Ser Pro Thr Leu Thr Trp Thr             100 105 110 Arg Trp Trp Leu Ser Trp Ser Ala Thr His Trp Ala Ser Val Arg Cys         115 120 125 Gly Cys Ser Met Pro Leu Ser Ala Gly Pro Arg Pro Ser Val Ser Gly     130 135 140 Ser Ser Cys Arg 145       <210> 354 <211> 20 <212> PRT <213> Homo sapiens    <400> 354 Arg Gln Arg Thr Gly Gly Arg Phe Trp Ala Arg Pro Trp Ala Ser Phe   1 5 10 15 Ala Ser Arg Ser              20       <210> 355 <211> 97 <212> PRT <213> Homo sapiens    <400> 355 Pro Ser Arg Ser Ser Leu Gln Val Pro His Ser Arg Ala Ser Trp Trp   1 5 10 15 Thr Ala Arg Trp Ser Ala Ser Ser Cys Thr Ser Pro Ser Thr Pro Ser              20 25 30 His Glu Trp Ser Ser Leu Thr Gly Pro Ala Ala Ala Cys Val Gly Arg          35 40 45 Ser Ala Ala Ser Thr Ala Ser Ser Arg Trp Arg Val Ala Gly Ala Thr      50 55 60 Ala Gly Pro Val Thr Ala Ser Gly Ser Gln Ser Thr Ser Ala Ser Ser  65 70 75 80 Trp Trp Asp Leu Gly Cys Met Asp Pro Ser Thr Gly Pro Pro Thr Thr                  85 90 95 Lys       <210> 356 <211> 65 <212> PRT <213> Homo sapiens    <400> 356 Thr Ser Arg Leu Phe Thr Pro Ile Ala Thr Pro Ser Trp Ala Arg Thr   1 5 10 15 Thr Arg Ala Ser Ala Ala Thr Ala Gln Pro Ala Pro Ser Ala Ser Cys              20 25 30 Ser Arg Ser Arg Trp Arg Cys Cys Pro Thr Ser Thr Thr Arg Pro Val          35 40 45 Pro Arg Ser Arg Ala Gln Thr Pro Thr Thr Ala Pro Lys Ala Cys Ala      50 55 60 Arg  65       <210> 357 <211> 52 <212> PRT <213> Homo sapiens    <400> 357 His Thr Ser Arg Pro Pro Arg Ala Pro Arg Pro Ala Ser Pro Phe Ala   1 5 10 15 Thr Arg Pro Gly Thr Thr Met Ala His Pro Trp Arg Thr Ala Arg Ser              20 25 30 Pro Arg Ser Ser Ser Thr Pro Arg Leu Pro Asp Thr Asp Thr Ala Leu          35 40 45 Pro Pro Trp Gly      50       <210> 358 <211> 120 <212> PRT <213> Homo sapiens    <400> 358 Pro Ser Pro Arg Pro Ser Ser Ala Ala Gly Ala Pro Pro Pro Arg Gly   1 5 10 15 Ala Arg Pro Ser Val Pro Gln Ala Val Cys Pro Leu His Ala Thr Phe              20 25 30 Leu Ser Ile Arg Thr Gly Leu Pro Cys Val His His Glu Cys Gly Cys          35 40 45 Trp Ile Arg Ala Ala Gly Glu Val Ala Arg Pro Val Ala Arg Pro Cys      50 55 60 Gly Asp Asn Pro Ser Gly Leu Gly Thr Gly Leu Cys Arg Pro Gly Pro  65 70 75 80 Gly Pro Thr Asp Pro Gln Leu Arg Ala Pro Ala His Val Val Cys Arg                  85 90 95 Arg Cys Ala Ala Gly Val Pro Arg Val Ser Ser Leu His Ile Ala Met             100 105 110 His Leu Arg Phe Pro Phe Leu Cys         115 120       <210> 359 <211> 68 <212> PRT <213> Homo sapiens    <400> 359 Glu Pro Ala Trp Val Ala Leu Leu Pro Glu Pro Trp Val Pro Asp Leu   1 5 10 15 Ala Phe Leu Leu Phe Leu Ser Val Tyr Gln Asp Thr Gly Pro Thr Cys              20 25 30 His Val Pro Glu Ala Thr Gln Ala Gln Pro Ala Gly Arg Ser His Cys          35 40 45 Leu Asp Ala Gly Leu Ser Ser Ala His Ala Gly Phe Ser Val Gly Thr      50 55 60 Ala Pro Ala Gly  65       <210> 360 <211> 5 <212> PRT <213> Homo sapiens    <400> 360 Pro Trp Pro Arg Trp   1 5       <210> 361 <211> 14 <212> PRT <213> Homo sapiens    <400> 361 Ala Val Cys Ser Val Arg Ser His Pro Pro Asp Gly Pro Arg   1 5 10       <210> 362 <211> 53 <212> PRT <213> Homo sapiens    <400> 362 Arg Pro Pro Leu Ser Ser Leu Pro Gly Arg Pro Ser Arg Ser Leu Gln   1 5 10 15 Pro Lys Met Gly Leu Arg Pro Cys Ala Pro Glu Leu Pro Cys Arg Arg              20 25 30 Met Gly Pro Gln Pro Ala Pro Thr Gly Ser Arg Ser Thr Ala Arg Leu          35 40 45 Tyr Ile Leu Leu Pro      50       <210> 363 <211> 33 <212> PRT <213> Homo sapiens    <400> 363 Pro Thr Trp Cys Arg Gly Ser His Pro Gln Val Leu Gly Ala Gln Ala   1 5 10 15 Pro Pro His Ser Gly Pro Arg Pro Pro Pro Thr Pro Arg Val Ser Ala              20 25 30 Leu       <210> 364 <211> 26 <212> PRT <213> Homo sapiens    <400> 364 Leu Leu Glu Pro Ala Ser Ser Pro Lys Pro Trp Glu Gly Cys Pro Pro   1 5 10 15 Gln Thr Met Pro Pro Asp Asp Phe Phe Lys              20 25       <210> 365 <211> 11 <212> PRT <213> Homo sapiens    <400> 365 Arg Asn Lys Cys Thr Cys Lys Lys Lys Lys Lys   1 5 10       <210> 366 <211> 7 <212> PRT <213> Homo sapiens    <400> 366 Ile Leu Phe Asn Thr Ser Phe   1 5       <210> 367 <211> 8 <212> PRT <213> Homo sapiens    <400> 367 Lys Asn Val Trp Lys Thr Asn Asp   1 5       <210> 368 <211> 39 <212> PRT <213> Homo sapiens    <400> 368 Ala Ser Arg Pro Met Val Ser Asn Gly Pro Arg Gln Phe Pro Gly Gln   1 5 10 15 Phe Tyr Cys Leu Gly Ser Trp Met Gly Phe Thr Ser Phe Phe Pro Arg              20 25 30 Thr Ser Gln Thr Glu Cys Glu          35       <210> 369 <211> 16 <212> PRT <213> Homo sapiens    <400> 369 Leu Asp Val Thr Glu Asn Asp Lys Lys Asp Cys Arg Gln Val Cys Lys   1 5 10 15       <210> 370 <211> 19 <212> PRT <213> Homo sapiens    <400> 370 Val Ile Leu Ile Ala Tyr Lys Tyr Glu Ile Gln Ser Val Cys Lys Gly   1 5 10 15 Val Phe Glu       <210> 371 <211> 30 <212> PRT <213> Homo sapiens    <400> 371 Gly Trp Cys Glu Cys Pro Cys Asp Trp Lys His Arg Val Thr Gly Lys   1 5 10 15 Lys Ile Ser Gly Ala Arg Glu Trp Gly Lys Val Arg Ser Val              20 25 30       <210> 372 <211> 6 <212> PRT <213> Homo sapiens    <400> 372 Met Phe Leu Ser Leu Cys   1 5       <210> 373 <211> 47 <212> PRT <213> Homo sapiens    <400> 373 Arg Val Arg Asp Gly Ser Gln Glu Gly Thr Ser Gly Gly Ser Thr Ala   1 5 10 15 Pro Pro Ala Ser Pro Asn Ala Leu Pro Thr Pro Leu His Thr Val Glu              20 25 30 Ala Val Asp Arg Ser Arg Arg Arg Asn Lys Gly His Pro His Ser          35 40 45       <210> 374 <211> 24 <212> PRT <213> Homo sapiens    <400> 374 Ala Ala Pro Trp Ser Ser Leu Ser Leu Thr Phe Leu Val Pro Gly Arg   1 5 10 15 Ser Asp Ser Gly Ala Ala Gln Glu              20       <210> 375 <211> 46 <212> PRT <213> Homo sapiens    <400> 375 Gly Cys Pro Leu Phe Leu Leu Arg Leu Leu Ser Thr Ala Ser Thr Val   1 5 10 15 Trp Ser Gly Val Gly Arg Ala Phe Gly Glu Ala Gly Gly Ala Val Asp              20 25 30 Pro Pro Asp Val Pro Ser Trp Glu Pro Ser Arg Thr Arg Tyr          35 40 45       <210> 376 <211> 8 <212> PRT <213> Homo sapiens    <400> 376 His Arg Leu Lys Asn Ile His Pro   1 5       <210> 377 <211> 39 <212> PRT <213> Homo sapiens    <400> 377 Thr Leu Leu Thr Leu Pro His Ser Leu Ala Pro Glu Ile Phe Phe Pro   1 5 10 15 Val Thr Arg Cys Phe Gln Ser His Gly His Ser His His Pro His Ser              20 25 30 Asn Thr Pro Leu His Thr Leu          35       <210> 378 <211> 52 <212> PRT <213> Homo sapiens    <400> 378 Ile Ser Tyr Leu Tyr Ala Ile Lys Ile Thr Gln Ser Ile Tyr Leu His   1 5 10 15 Thr Cys Arg Gln Ser Phe Leu Ser Phe Ser Val Thr Ser Ser His Ser              20 25 30 His Ser Val Trp Asp Val Leu Gly Lys Lys Glu Val Lys Pro Ile Gln          35 40 45 Glu Pro Arg Gln      50       <210> 379 <211> 24 <212> PRT <213> Homo sapiens    <400> 379 Asn Cys Pro Gly Asn Cys Leu Gly Pro Leu Leu Thr Ile Gly Leu Glu   1 5 10 15 Ala Gln His Tyr Pro His Ile Tyr              20       <210> 380 <211> 6 <212> PRT <213> Homo sapiens    <400> 380 Met Ser Gly Thr Arg Thr   1 5       <210> 381 <211> 27 <212> PRT <213> Homo sapiens    <400> 381 Pro Arg Gln Thr Gly His Asp Phe Gln Gly Ala His Asn Gly Val Ser   1 5 10 15 Ser Gly Phe Leu Met Asp Leu Ile Lys Gly Pro              20 25       <210> 382 <211> 20 <212> PRT <213> Homo sapiens    <400> 382 Leu Ser Leu Leu Pro Phe Leu His Thr Ala Cys Tyr Ile Lys Phe Leu   1 5 10 15 Ser Arg Leu Met              20       <210> 383 <211> 52 <212> PRT <213> Homo sapiens    <400> 383 Val Thr Gly Ser Asp Pro Ile Cys Gln Ser Leu Pro Gly Pro His Leu   1 5 10 15 Asn Ser Val Leu Phe Asn Ala Phe Leu Ser Leu Pro Leu Pro Ser Gln              20 25 30 Glu Ala Phe Ile Gly Lys Gly Leu Ser Gly Ser Pro His Pro Leu Pro          35 40 45 Ile Pro Ser Phe      50       <210> 384 <211> 5 <212> PRT <213> Homo sapiens    <400> 384 Ala Arg Gly Gly Ala   1 5       <210> 385 <211> 34 <212> PRT <213> Homo sapiens    <400> 384 Ser Asp Cys Trp Ser Gln Pro Leu Ala Cys Pro Arg Ile Leu Cys Leu   1 5 10 15 Ser Leu Arg Thr Trp His Phe Ser Arg Thr Ser Trp Lys Ala Cys Ser              20 25 30 Gly Val       <210> 386 <211> 31 <212> PRT <213> Homo sapiens    <400> 386 Lys Thr Lys Ser Thr Val Glu Trp Ala Arg Met Ala Arg Cys Cys Pro   1 5 10 15 Pro Arg Ser Ser Arg Asp Ser Trp Leu Ala Met Trp Trp Pro Asn              20 25 30       <210> 387 <211> 30 <212> PRT <213> Homo sapiens    <400> 387 Gly His Gln Gln Tyr Trp Ala Leu Leu Trp Ala Pro Ala Leu Ala Ser   1 5 10 15 Met Arg Leu Arg His Met Leu Cys Pro Thr Trp Arg Arg His              20 25 30       <210> 388 <211> 75 <212> PRT <213> Homo sapiens    <400> 388 Gly Thr Ile Cys Ser Cys Tyr Ala Arg Gly Pro Thr Ser Ser Arg Cys   1 5 10 15 His Gly Arg Gly Arg Met Ser Ser Ser Ala Phe Arg Trp Arg His Phe              20 25 30 Ile Trp Ile Pro Gln Leu Ser Ser Ile Cys Tyr Leu Gln Leu Ser Cys          35 40 45 His Leu His Pro Cys Leu Pro Ser Cys Arg Leu Trp Thr Val Val Pro      50 55 60 Gln Pro Ala Pro Trp Ile Pro Ser Ser Pro Ser  65 70 75       <210> 389 <211> 21 <212> PRT <213> Homo sapiens    <400> 389 Leu His Gly Thr Arg Pro Lys Thr Val Ala Ser Arg Thr Thr Ser Pro   1 5 10 15 Leu Leu Phe Lys Pro              20       <210> 390 <211> 37 <212> PRT <213> Homo sapiens    <400> 390 Met Pro Leu Ile Leu Ser Ile Leu Ser Gly Asn Val Pro Arg Leu Leu   1 5 10 15 Leu Pro Gly Ser Trp Leu His Asn Leu Ile Phe Pro Lys Arg Val Ala              20 25 30 Ile Pro Ala Ala Pro          35       <210> 391 <211> 64 <212> PRT <213> Homo sapiens    <400> 391 Pro Pro Arg Val Leu Cys Gly Tyr Glu Cys Arg Gly Trp Gly Tyr Ala   1 5 10 15 Arg Pro Gly Pro Ser Gln Ala Gly Pro Leu Asp Pro Asp Ala Thr Pro              20 25 30 Ile His Cys His Val Arg Cys Pro Cys Pro Ile Ala Gly Thr Val Pro          35 40 45 Cys Gly Arg Pro Ser Ala Leu Pro Ala Leu Leu Ser Arg Ala Ala Asp      50 55 60       <210> 392 <211> 40 <212> PRT <213> Homo sapiens    <400> 392 Ala Asp Gln Ala Thr Val Met Arg Leu Leu Pro Ser Gly Arg Leu Ala   1 5 10 15 Ser Met Ala Pro Gly Ala Pro Thr Leu Ala Pro Gly Cys Ser Leu Arg              20 25 30 Thr Ile Ser Pro Ala Leu Trp Arg          35 40       <210> 393 <211> 20 <212> PRT <213> Homo sapiens    <400> 393 Gln Gln Pro Gly Asp Leu Ser Ser Ala Leu His Gly Pro Gln His Leu   1 5 10 15 Pro Gly Ala Glu              20       <210> 394 <211> 238 <212> PRT <213> Homo sapiens    <400> 394 Ser Gln Asp Trp Lys His Ser Cys Ala Leu Leu Pro Leu Pro Pro Ala   1 5 10 15 Pro Pro Leu Cys Ala Ser Gly Val Ser Ala Ala Ala Ala Asp Gly Cys              20 25 30 Gly Ser Leu Leu Cys Ser Arg Gly Pro Ser Ser Ser Arg Glu His Pro          35 40 45 Ser Gln Ser Pro Ser Ser Ser Cys Cys Gln Pro His Ala Pro Ala Tyr      50 55 60 His Ser Ala Arg Pro Ala Ala Pro His Ser Val Leu Pro His Leu Arg  65 70 75 80 Leu Val Val Ser Val His Arg Ala Ala His Glu Ala Thr Ala Ala Ala                  85 90 95 Pro Gly Thr Ser Glu Pro Leu Pro Leu His Phe Trp Cys Ala Ser Glu             100 105 110 Ser Arg Ser Ala Cys Trp Arg Arg Leu Trp Pro Arg Pro Pro Gly Arg         115 120 125 Phe Leu Arg Met Gly Ser Thr Arg Gly Ala Glu Pro Gly Thr Lys Trp     130 135 140 Thr Ala His Val Cys Cys His Glu Ala Trp Gln Gln His His Thr Pro 145 150 155 160 Leu Cys Gly Val Leu Leu Ala Gly Gly Gln Arg Arg Ala Leu Ser Ser                 165 170 175 Pro Ala Thr Ala Ala Ala His Ser Arg Leu Leu Pro Gly His Ile Ala             180 185 190 His Trp Pro Gly His Ala Pro Val Leu Trp Gln Pro Leu Val Pro Asp         195 200 205 Asn Phe His Pro Asp Ser Gly Pro Cys Arg Leu Gly Ala Thr Thr Arg     210 215 220 Ser Pro Ser Gln Ala Phe Leu Pro Leu Pro Ser Ala Ala Leu 225 230 235       <210> 395 <211> 35 <212> PRT <213> Homo sapiens    <400> 395 Gln Val Pro Cys Glu Lys Ser Trp Arg Ser Glu Gly Ser Gln Val Ile   1 5 10 15 Leu Trp Arg Leu Val Asp Glu Gly Val Pro Leu Gly Asp Val Lys Cys              20 25 30 Gly Phe Gly          35       <210> 396 <211> 19 <212> PRT <213> Homo sapiens    <400> 396 Gly Asn Ala Tyr His Pro Pro Pro Pro Thr Lys Phe Phe Gln Thr Lys   1 5 10 15 Glu Leu Arg       <210> 397 <211> 40 <212> PRT <213> Homo sapiens    <400> 397 His Gln Tyr Leu Gly Leu Arg Asn Asn Pro Ile Leu Val Gly Gln Leu   1 5 10 15 Pro Ala Leu Ser Cys Met Asn Arg Val Asp Glu Ser Gly Val Trp Ala              20 25 30 Thr Ser Gly Phe Pro Cys Leu Leu          35 40       <210> 398 <211> 9 <212> PRT <213> Homo sapiens    <400> 398 Ser Pro Ser Arg Ala Thr Gly Ala Gly   1 5       <210> 399 <211> 46 <212> PRT <213> Homo sapiens    <400> 399 Ser Ser Pro Ala Met Val His Asp Ser Ser Ile Arg Asp Pro His Pro   1 5 10 15 Ser Thr Phe Met Gln Glu Gly Pro Val Ala Thr Asp Tyr Thr Thr Ile              20 25 30 Thr Gln Thr Thr Leu Thr Val Ser Ser Ser Ser Ser Asn Ala          35 40 45       <210> 400 <211> 14 <212> PRT <213> Homo sapiens    <400> 400 Arg His Ala Pro Cys Pro Leu His Ser Ala Ala Pro His Thr   1 5 10       <210> 401 <211> 24 <212> PRT <213> Homo sapiens    <400> 401 Pro Leu Phe Trp Lys Pro Gln Arg Gly Leu Gly Leu Thr His Leu Arg   1 5 10 15 Glu Cys Ser Pro Trp Ala Leu Ala              20       <210> 402 <211> 20 <212> PRT <213> Homo sapiens    <400> 402 Ala Asp Thr Pro Asp Leu Ser Val His Pro Glu Gly Cys Leu Glu Ala   1 5 10 15 Arg Tyr Pro Leu              20       <210> 403 <211> 28 <212> PRT <213> Homo sapiens    <400> 403 Glu Val Pro Cys Phe Pro Leu Trp Gly Leu Pro Leu Pro Ser Ser Leu   1 5 10 15 Pro Ala Pro Asn Ser Leu Gly Lys Leu Cys Thr Glu              20 25       <210> 404 <211> 15 <212> PRT <213> Homo sapiens    <400> 404 Pro Glu Thr Arg Tyr Arg Lys Pro Val Ala Gln Ser Val Ser Leu   1 5 10 15       <210> 405 <211> 6 <212> PRT <213> Homo sapiens    <400> 405 Asp Leu Asn Lys Val Phe   1 5       <210> 406 <211> 16 <212> PRT <213> Homo sapiens    <400> 406 Ala Val Gly Trp Phe Leu Gln Pro Gln Pro Lys Lys Lys Lys Lys Lys   1 5 10 15       <210> 407 <211> 22 <212> PRT <213> Homo sapiens    <400> 407 Phe Tyr Ser Thr His His Ser Glu Arg Thr Cys Gly Lys Leu Met Thr   1 5 10 15 Glu Leu Leu Asp Gln Trp              20       <210> 408 <211> 36 <212> PRT <213> Homo sapiens    <400> 408 Val Met Asp Arg Gly Ser Phe Leu Asp Asn Phe Ile Val Leu Val Pro   1 5 10 15 Gly Trp Ala Leu Pro Leu Ser Ser Gln Gly His Pro Lys Leu Asn Val              20 25 30 Ser Asp Trp Met          35       <210> 409 <211> 17 <212> PRT <213> Homo sapiens    <400> 409 Leu Arg Met Thr Lys Lys Thr Val Gly Lys Cys Val Ser Lys Trp Thr   1 5 10 15 Glu       <210> 410 <211> 43 <212> PRT <213> Homo sapiens    <400> 410 Ser His Ile Ser Met Lys Phe Arg Val Tyr Ala Lys Glu Cys Leu Asn   1 5 10 15 Glu Gly Gly Val Ser Val Arg Val Ile Gly Asn Ile Val Ser Leu Gly              20 25 30 Arg Lys Phe Arg Glu Leu Gly Asn Gly Val Lys          35 40       <210> 411 <211> 8 <212> PRT <213> Homo sapiens    <400> 411 Gly Val Phe Lys Gly Glu Cys Phe   1 5       <210> 412 <211> 61 <212> PRT <213> Homo sapiens    <400> 412 Val Cys Ala Ser Asn Gly Phe Val Met Val Pro Arg Arg Gly His Leu   1 5 10 15 Gly Asp Pro Arg Leu Leu Pro Pro Arg Arg Met Leu Ser Pro His His              20 25 30 Ser Thr Leu Leu Arg Gln Leu Thr Gly Ala Ala Glu Glu Thr Arg Asp          35 40 45 Ile Leu Thr Pro Glu Pro Leu Arg Gly Leu His Ser Pro      50 55 60       <210> 413 <211> 77 <212> PRT <213> Homo sapiens    <400> 413 Phe Arg Gly Glu Ala Thr Leu Glu Arg Leu Arg Ser Glu Asp Val Pro   1 5 10 15 Cys Phe Phe Cys Gly Ser Cys Gln Leu Pro Gln Gln Cys Gly Val Val              20 25 30 Trp Gly Glu His Ser Ala Arg Arg Glu Glu Pro Trp Ile Pro Gln Met          35 40 45 Ser Pro Pro Gly Asn His His Glu Pro Val Thr Ser Thr Asp Ser Lys      50 55 60 Thr Phe Thr Leu Lys His Ser Ser Leu Tyr Pro Ile Pro  65 70 75       <210> 414 <211> 7 <212> PRT <213> Homo sapiens    <400> 414 Leu Pro Lys Phe Ser Ser Gln   1 5       <210> 415 <211> 66 <212> PRT <213> Homo sapiens    <400> 415 His Asp Val Ser Asn His Thr Asp Thr His Thr Thr Leu Ile Gln Thr   1 5 10 15 Leu Leu Cys Ile His Ser Glu Phe His Thr Tyr Met Arg Ser Lys Ser              20 25 30 Leu Ser Pro Phe Thr Tyr Thr Leu Ala Asp Ser Leu Phe Cys His Ser          35 40 45 Gln Ser His Pro Val Thr His Ile Gln Phe Gly Met Ser Leu Gly Arg      50 55 60 Lys Arg  65       <210> 416 <211> 23 <212> PRT <213> Homo sapiens    <400> 416 Ser Pro Ser Arg Asn Gln Asp Asn Lys Ile Val Gln Glu Thr Ala Ser   1 5 10 15 Val His Tyr Ser Pro Leu Val              20       <210> 417 <211> 37 <212> PRT <213> Homo sapiens    <400> 417 Lys Leu Ser Ile Thr His Thr Phe Thr Lys Cys Gln Ala Leu Glu His   1 5 10 15 Ser Ser Gln Asp Arg Leu Val Thr Thr Phe Lys Glu Leu Ile Met Glu              20 25 30 Ser Val Val Val Ser          35       <210> 418 <211> 17 <212> PRT <213> Homo sapiens    <400> 418 Leu Lys Val Pro Ser Cys Pro Ser Cys Leu Ser Tyr Ile Leu Leu Ala   1 5 10 15 Ile       <210> 419 <211> 5 <212> PRT <213> Homo sapiens    <400> 419 Asn Ser Cys Gln Gly   1 5       <210> 420 <211> 17 <212> PRT <213> Homo sapiens    <400> 420 Cys Lys Leu Leu Val Gln Ile Pro Ser Val Ser Pro Phe Leu Ala Leu   1 5 10 15 Ile       <210> 421 <211> 19 <212> PRT <213> Homo sapiens    <400> 421 Ile Leu Cys Phe Ser Met Leu Phe Phe Leu Cys His Cys His Leu Arg   1 5 10 15 Lys Leu Leu       <210> 422 <211> 41 <212> PRT <213> Homo sapiens    <400> 422 Glu Lys Val Phe Leu Ala His Pro Ile Pro Ser Gln Phe Pro Ala Ser   1 5 10 15 Asp Gly Ile Glu Gln Gly Val Gly Leu Ser Gln Thr Ala Gly Ala Ser              20 25 30 Leu Ser Leu Val Leu Gly Phe Ser Ala          35 40       <210> 423 <211> 101 <212> PRT <213> Homo sapiens    <400> 423 Gly Pro Gly Ile Ser Gln Glu Pro Ala Gly Lys Pro Ala Ala Ala Cys   1 5 10 15 Arg Arg Arg Ser Gln Gln Trp Ser Gly Pro Gly Trp Leu Ala Val Val              20 25 30 Leu Pro Val Pro Gln Gly Ile Pro Gly Trp Leu Cys Gly Gly Gln Thr          35 40 45 Glu Gly Ile Ser Ser Ile Gly Leu Cys Cys Gly His Leu His Trp His      50 55 60 Leu Cys Gly Ser Gly Ile Cys Cys Ala Gln Arg Gly Glu Asp Ile Lys  65 70 75 80 Gly Leu Phe Ala Val Ala Thr Gln Gly Ala Arg Leu Ala Leu Gly Ala                  85 90 95 Met Glu Glu Ala Gly             100       <210> 424 <211> 39 <212> PRT <213> Homo sapiens    <400> 424 Ala Ala Gln Pro Ser Gly Gly Asp Thr Leu Ser Gly Phe Pro Ser Cys   1 5 10 15 His Pro Phe Ala Ile Ser Asn Phe Pro Ala Thr Phe Ile Leu Ala Ser              20 25 30 Leu Pro Ala Asp Cys Gly Gln          35       <210> 425 <211> 43 <212> PRT <213> Homo sapiens    <400> 425 Phe Leu Ser Leu His Pro Gly Phe Leu Leu Pro Leu Pro Ser Ser Met   1 5 10 15 Gly Leu Ala Pro Arg Leu Trp Leu Gln Gly Pro Pro Ala Pro Tyr Ser              20 25 30 Ser Ser Pro Asp Cys Gly Val Gly Arg Cys Leu          35 40       <210> 426 <211> 21 <212> PRT <213> Homo sapiens    <400> 426 Ser Ser Val Phe Ser Leu Ala Met Phe His Gly Phe Ser Phe Leu Gly   1 5 10 15 Ala Gly Ser Ile Thr              20       <210> 427 <211> 344 <212> PRT <213> Homo sapiens    <400> 427 Phe Ser Pro Asn Val Leu Gln Ser Leu Leu Pro Leu Ser His Pro Gly   1 5 10 15 Ser Cys Val Gly Met Ser Val Glu Asp Gly Gly Met Pro Gly Leu Gly              20 25 30 Arg Pro Arg Gln Ala Arg Trp Thr Leu Met Leu Leu Leu Ser Thr Ala          35 40 45 Met Tyr Gly Ala His Ala Pro Leu Leu Ala Leu Cys His Val Asp Gly      50 55 60 Arg Val Pro Phe Arg Pro Ser Ser Ala Val Leu Leu Thr Glu Leu Thr  65 70 75 80 Lys Leu Leu Leu Cys Ala Phe Ser Leu Leu Val Gly Trp Gln Ala Trp                  85 90 95 Pro Gln Gly Pro Pro Pro Trp Arg Gln Ala Ala Pro Phe Ala Leu Ser             100 105 110 Ala Leu Leu Tyr Gly Ala Asn Asn Asn Leu Val Ile Tyr Leu Gln Arg         115 120 125 Tyr Met Asp Pro Ser Thr Tyr Gln Val Leu Ser Asn Leu Lys Ile Gly     130 135 140 Ser Thr Ala Val Leu Tyr Cys Leu Cys Leu Arg His Arg Leu Ser Val 145 150 155 160 Arg Gln Gly Leu Ala Leu Leu Leu Leu Met Ala Ala Gly Ala Cys Tyr                 165 170 175 Ala Ala Gly Gly Leu Gln Val Pro Gly Asn Thr Leu Pro Ser Pro Pro             180 185 190 Pro Ala Ala Ala Ala Ser Pro Met Pro Leu His Ile Thr Pro Leu Gly         195 200 205 Leu Leu Leu Leu Ile Leu Tyr Cys Leu Ile Ser Gly Leu Ser Ser Val     210 215 220 Tyr Thr Glu Leu Leu Met Lys Arg Gln Arg Leu Pro Leu Ala Leu Gln 225 230 235 240 Asn Leu Phe Leu Tyr Thr Phe Gly Val Leu Leu Asn Leu Gly Leu His                 245 250 255 Ala Gly Gly Gly Ser Gly Pro Gly Leu Leu Glu Gly Phe Ser Gly Trp             260 265 270 Ala Ala Leu Val Val Leu Ser Gln Ala Leu Asn Gly Leu Leu Met Ser         275 280 285 Ala Val Met Lys His Gly Ser Ser Ile Thr Arg Leu Phe Val Val Ser     290 295 300 Cys Ser Leu Val Val Asn Ala Val Leu Ser Ala Val Leu Leu Arg Leu 305 310 315 320 Gln Leu Thr Ala Ala Phe Phe Leu Ala Thr Leu Leu Ile Gly Leu Ala                 325 330 335 Met Arg Leu Tyr Tyr Gly Ser Arg             340       <210> 428 <211> 60 <212> PRT <213> Homo sapiens    <400> 428 Ser Leu Thr Thr Ser Thr Leu Ile Pro Asp Pro Val Asp Trp Ala Pro   1 5 10 15 Pro Pro Asp Pro Pro Pro Arg Pro Ser Ser Leu Ser His Gln Gln Pro              20 25 30 Cys Asn Lys Cys Leu Val Arg Lys Ala Gly Glu Val Arg Ala Ala Arg          35 40 45 Leu Phe Ser Gly Gly Trp Trp Met Lys Gly Tyr Pro      50 55 60       <210> 429 <211> 23 <212> PRT <213> Homo sapiens    <400> 429 Ser Val Gly Leu Val Lys Glu Met Leu Thr Ile Pro His Pro Gln Pro   1 5 10 15 Ser Ser Ser Arg Leu Lys Asn              20       <210> 430 <211> 5 <212> PRT <213> Homo sapiens    <400> 430 Gly Asn Ile Asn Thr   1 5       <210> 431 <211> 15 <212> PRT <213> Homo sapiens    <400> 431 Glu Ile Thr Pro Ser Leu Leu Gly Ser Ser Leu Leu Cys Pro Ala   1 5 10 15       <210> 432 <211> 39 <212> PRT <213> Homo sapiens    <400> 432 Thr Glu Leu Met Lys Val Gly Cys Gly Gln Gln Val Ala Phe Leu Ala   1 5 10 15 Tyr Phe Ser His Pro Ala Glu Pro Leu Glu Leu Ala Ser Pro Ala Gln              20 25 30 Pro Trp Cys Met Thr Leu Pro          35       <210> 433 <211> 25 <212> PRT <213> Homo sapiens    <400> 433 Gly Ile Leu Thr Leu Pro Leu Ser Cys Lys Lys Ala Gln Leu Pro Gln   1 5 10 15 Ile Ile Gln Pro Leu Pro Lys Pro Leu              20 25       <210> 434 <211> 36 <212> PRT <213> Homo sapiens    <400> 434 Gln Ser Pro Pro Val Pro Ala Met Pro Arg Asp Met Leu Pro Ala Leu   1 5 10 15 Ser Thr Val Leu Leu Pro Thr Pro Ser Leu Cys Ser Gly Asn Pro Arg              20 25 30 Glu Gly Trp Ala          35       <210> 435 <211> 74 <212> PRT <213> Homo sapiens    <400> 435 Leu Ile Ser Gly Asn Val Ala Pro Gly Pro Trp Leu Lys Pro Thr Leu   1 5 10 15 Leu Thr Ser Leu Phe Thr Leu Arg Ala Val Leu Lys Pro Ala Thr His              20 25 30 Ser Glu Ala Pro Arg Arg Tyr His Ala Ser His Ser Gly Ala Cys Pro          35 40 45 Cys Leu Ala Val Ser Gln Leu Pro Thr Ala Trp Gly Ser Ser Ala Gln      50 55 60 Ser Asp Leu Arg Pro Gly Thr Gly Asn Leu  65 70       <210> 436 <211> 20 <212> PRT <213> Homo sapiens    <400> 436 Leu Asn Gln Cys Leu Phe Asn Cys Ile Ser Asn Lys Ile Leu Ile Lys   1 5 10 15 Ser Ser Arg Leu              20       <210> 437 <211> 13 <212> PRT <213> Homo sapiens    <400> 437 Gly Gly Ser Tyr Asn His Ser Gln Lys Lys Lys Lys Lys   1 5 10       <210> 438 <211> 13 <212> PRT <213> Homo sapiens    <400> 438 Phe Ile Gln His Ile Ile Leu Lys Glu Arg Val Glu Asn   1 5 10       <210> 439 <211> 28 <212> PRT <213> Homo sapiens    <400> 439 Trp Thr Glu Ala Val Ser Trp Thr Ile Leu Leu Ser Trp Phe Leu Asp   1 5 10 15 Gly Leu Tyr Leu Phe Leu Pro Lys Asp Ile Pro Asn              20 25       <210> 440 <211> 5 <212> PRT <213> Homo sapiens    <400> 440 Val Thr Gly Cys Asp   1 5       <210> 441 <211> 8 <212> PRT <213> Homo sapiens    <400> 441 Gln Lys Arg Leu Ser Ala Ser Val   1 5       <210> 442 <211> 10 <212> PRT <213> Homo sapiens    <400> 442 Val Asn Gly Leu Ser Asp Phe Asp Arg Ile   1 5 10       <210> 443 <211> 9 <212> PRT <213> Homo sapiens    <400> 443 Asn Ser Glu Cys Met Gln Arg Ser Val   1 5       <210> 444 <211> 13 <212> PRT <213> Homo sapiens    <400> 444 Leu Glu Thr Ser Cys His Trp Glu Glu Asn Phe Gly Ser   1 5 10       <210> 445 <211> 18 <212> PRT <213> Homo sapiens    <400> 445 Ser Glu Glu Cys Leu Arg Val Asn Val Phe Glu Ser Val Leu Val Thr   1 5 10 15 Gly Ser       <210> 446 <211> 27 <212> PRT <213> Homo sapiens    <400> 446 Trp Phe Pro Gly Gly Asp Ile Trp Gly Ile His Gly Ser Ser Arg Leu   1 5 10 15 Ala Glu Cys Ser Pro His Thr Thr Pro His Cys              20 25       <210> 447 <211> 216 <212> PRT <213> Homo sapiens    <400> 447 Gln Glu Pro Gln Lys Lys Gln Gly Thr Ser Ser Leu Leu Ser Arg Ser   1 5 10 15 Val Val Phe Thr Leu Leu Asp Leu Phe Ser Ser Gly Glu Lys Arg Leu              20 25 30 Trp Ser Gly Ser Gly Val Arg Met Ser Leu Val Ser Ser Ala Ala Pro          35 40 45 Val Asn Cys Leu Asn Ser Val Glu Trp Cys Gly Glu Ser Ile Arg Arg      50 55 60 Gly Gly Arg Ser Arg Gly Ser Pro Arg Cys Pro Leu Leu Gly Thr Ile  65 70 75 80 Thr Asn Pro Leu Leu Ala Gln Thr Gln Lys His Ser Pro Leu Asn Thr                  85 90 95 Pro His Phe Thr Pro Phe Pro Ser Ser Arg Asn Phe Leu Pro Ser Asp             100 105 110 Thr Met Phe Pro Ile Thr Arg Thr Leu Thr Pro Pro Ser Phe Lys His         115 120 125 Ser Phe Ala Tyr Thr Leu Asn Phe Ile Leu Ile Cys Asp Gln Asn His     130 135 140 Ser Val His Leu Leu Thr His Leu Pro Thr Val Phe Phe Val Ile Leu 145 150 155 160 Ser His Ile Gln Ser Leu Thr Phe Ser Leu Gly Cys Pro Trp Glu Glu                 165 170 175 Arg Gly Lys Ala His Pro Gly Thr Lys Thr Ile Lys Leu Ser Arg Lys             180 185 190 Leu Pro Arg Ser Ile Thr His His Trp Ser Arg Ser Ser Ala Leu Pro         195 200 205 Thr His Leu Leu Asn Val Arg His     210 215       <210> 448 <211> 15 <212> PRT <213> Homo sapiens    <400> 448 Asn Ile Val Ala Lys Thr Asp Trp Ser Arg Leu Ser Arg Ser Ser   1 5 10 15       <210> 449 <211> 7 <212> PRT <213> Homo sapiens    <400> 449 Trp Phe Pro Asp Gly Pro Asn   1 5       <210> 450 <211> 97 <212> PRT <213> Homo sapiens    <400> 450 Arg Ser Leu Ala Val Pro Pro Ala Phe Pro Thr Tyr Cys Leu Leu Tyr   1 5 10 15 Lys Ile Leu Val Lys Val Asp Val Ser Tyr Trp Phe Arg Ser His Leu              20 25 30 Ser Val Pro Ser Trp Pro Ser Phe Glu Phe Cys Ala Phe Gln Cys Phe          35 40 45 Ser Phe Phe Ala Thr Ala Ile Ser Gly Ser Phe Tyr Arg Lys Arg Ser      50 55 60 Phe Trp Leu Thr Pro Ser Pro Pro Asn Ser Gln Leu Leu Met Glu Leu  65 70 75 80 Ser Lys Gly Trp Gly Leu Val Arg Leu Leu Glu Pro Ala Ser Arg Leu                  85 90 95 Ser       <210> 451 <211> 98 <212> PRT <213> Homo sapiens    <400> 451 Asp Ser Leu Pro Lys Leu Lys Asp Leu Ala Phe Leu Lys Asn Gln Leu   1 5 10 15 Glu Ser Leu Gln Arg Arg Val Glu Asp Glu Val Asn Ser Gly Val Gly              20 25 30 Gln Asp Gly Ser Leu Leu Ser Ser Pro Phe Leu Lys Gly Phe Leu Ala          35 40 45 Gly Tyr Val Val Ala Lys Leu Arg Ala Ser Ala Val Leu Gly Phe Ala      50 55 60 Val Gly Thr Cys Thr Gly Ile Tyr Ala Ala Gln Ala Tyr Ala Val Pro  65 70 75 80 Asn Val Glu Lys Thr Leu Arg Asp Tyr Leu Gln Leu Leu Arg Lys Gly                  85 90 95 Pro Asp       <210> 452 <211> 111 <212> PRT <213> Homo sapiens    <400> 452 Val Pro Trp Lys Arg Gln Asp Glu Gln Leu Ser Leu Gln Val Glu Thr   1 5 10 15 Leu Tyr Leu Asp Ser Pro Ala Val Ile His Leu Leu Ser Pro Thr Phe              20 25 30 Leu Pro Pro Ser Ser Leu Pro Pro Phe Leu Gln Ile Val Asp Ser Ser          35 40 45 Ser Ser Ala Cys Thr Leu Asp Ser Phe Phe Pro Phe Leu Ala Pro Trp      50 55 60 Asp Ser Pro Gln Asp Cys Gly Phe Lys Asp His Gln Pro Leu Thr Leu  65 70 75 80 Gln Ala Leu Thr Val Glu Leu Val Asp Ala Ser Asp Pro Gln Tyr Ser                  85 90 95 Leu Trp Gln Cys Ser Thr Ala Ser Pro Ser Trp Glu Leu Ala Pro             100 105 110       <210> 453 <211> 22 <212> PRT <213> Homo sapiens    <400> 453 Leu Asp Phe Pro Gln Thr Cys Cys Asn Pro Cys Cys Pro Leu Ala Thr   1 5 10 15 Gln Gly Leu Val Trp Val              20       <210> 454 <211> 17 <212> PRT <213> Homo sapiens    <400> 454 Arg Met Gly Val Cys Gln Ala Trp Ala Val Pro Gly Arg Pro Ala Gly   1 5 10 15 Pro       <210> 455 <211> 34 <212> PRT <213> Homo sapiens    <400> 455 Cys Tyr Ser Tyr Pro Leu Pro Cys Thr Val Pro Met Pro His Cys Trp   1 5 10 15 His Cys Ala Met Trp Thr Ala Glu Cys Pro Ser Gly Pro Pro Gln Pro              20 25 30 Cys Cys       <210> 456 <211> 11 <212> PRT <213> Homo sapiens    <400> 456 Pro Ser Tyr Cys Tyr Ala Pro Ser Pro Phe Trp   1 5 10       <210> 457 <211> 31 <212> PRT <213> Homo sapiens    <400> 457 Ala Gly Lys His Gly Pro Arg Gly Pro His Pro Gly Ala Arg Leu Leu   1 5 10 15 Pro Ser His Tyr Gln Pro Cys Ser Met Ala Leu Thr Thr Thr Trp              20 25 30       <210> 458 <211> 14 <212> PRT <213> Homo sapiens    <400> 458 Ser Ile Phe Ser Val Thr Trp Thr Pro Ala Pro Thr Arg Cys   1 5 10       <210> 459 <211> 25 <212> PRT <213> Homo sapiens    <400> 459 Val Ile Ser Arg Leu Glu Ala Gln Leu Cys Ser Thr Ala Ser Ala Ser   1 5 10 15 Gly Thr Ala Ser Leu Cys Val Arg Gly              20 25       <210> 460 <211> 37 <212> PRT <213> Homo sapiens    <400> 460 Trp Leu Arg Glu Pro Ala Met Gln Gln Gly Ala Phe Lys Phe Pro Gly   1 5 10 15 Thr Pro Phe Pro Val Pro Leu Gln Gln Leu Leu Pro Ala Pro Cys Pro              20 25 30 Cys Ile Ser Leu Arg          35       <210> 461 <211> 22 <212> PRT <213> Homo sapiens    <400> 461 Ala Cys Cys Ser Ser Phe Cys Thr Ala Ser Ser Gln Ala Cys Arg Gln   1 5 10 15 Cys Thr Gln Ser Cys Ser              20       <210> 462 <211> 20 <212> PRT <213> Homo sapiens    <400> 462 Ser Asp Ser Gly Cys Pro Trp His Phe Arg Thr Ser Ser Ser Thr Leu   1 5 10 15 Leu Val Cys Phe              20       <210> 463 <211> 24 <212> PRT <213> Homo sapiens    <400> 463 Val Cys Met Leu Ala Ala Ala Leu Ala Gln Ala Ser Trp Lys Val Ser   1 5 10 15 Gln Asp Gly Gln His Ser Trp Cys              20       <210> 464 <211> 8 <212> PRT <213> Homo sapiens    <400> 464 Met Asp Cys Ser Cys Leu Leu Ser   1 5       <210> 465 <211> 55 <212> PRT <213> Homo sapiens    <400> 465 Ser Met Ala Ala Ala Ser His Ala Ser Leu Trp Cys Pro Ala Arg Trp   1 5 10 15 Trp Ser Thr Pro Cys Ser Gln Gln Ser Cys Tyr Gly Cys Ser Ser Gln              20 25 30 Pro Pro Ser Ser Trp Pro His Cys Ser Leu Ala Trp Pro Cys Ala Cys          35 40 45 Thr Met Ala Ala Ala Ser Pro      50 55       <210> 466 <211> 25 <212> PRT <213> Homo sapiens    <400> 466 Ile Gly Arg His His Gln Ile Pro Leu Pro Gly Leu Pro Pro Ser Pro   1 5 10 15 Ile Ser Ser Pro Val Thr Ser Ala Leu              20 25       <210> 467 <211> 5 <212> PRT <213> Homo sapiens    <400> 467 Glu Lys Leu Glu Lys   1 5       <210> 468 <211> 11 <212> PRT <213> Homo sapiens    <400> 468 Gly Gln Pro Gly Tyr Ser Leu Glu Val Gly Gly   1 5 10       <210> 469 <211> 28 <212> PRT <213> Homo sapiens    <400> 469 Arg Gly Thr Pro Arg Arg Cys Glu Val Trp Val Trp Leu Arg Lys Cys   1 5 10 15 Leu Pro Ser Pro Thr Pro Asn Gln Val Leu Pro Asp              20 25       <210> 470 <211> 12 <212> PRT <213> Homo sapiens    <400> 470 Arg Ile Lys Val Thr Ser Ile Pro Arg Pro Glu Lys   1 5 10       <210> 471 <211> 16 <212> PRT <213> Homo sapiens    <400> 471 Pro His Pro Cys Trp Ala Ala Pro Cys Phe Val Leu His Glu Gln Ser   1 5 10 15       <210> 472 <211> 31 <212> PRT <213> Homo sapiens    <400> 472 Lys Trp Gly Val Gly Asn Lys Trp Leu Ser Leu Pro Thr Leu Val Thr   1 5 10 15 Gln Gln Ser His Trp Ser Trp Leu Val Gln Pro Ser His Gly Ala              20 25 30       <210> 473 <211> 72 <212> PRT <213> Homo sapiens    <400> 473 Leu Phe His Lys Gly Ser Ser Pro Phe His Phe His Ala Arg Arg Pro   1 5 10 15 Ser Cys His Arg Leu Tyr Asn His Tyr Pro Asn His Ser Asp Ser Leu              20 25 30 Leu Gln Phe Gln Gln Cys Leu Glu Thr Cys Ser Leu Pro Ser Pro Gln          35 40 45 Cys Cys Ser Pro His Leu Ala Phe Val Leu Glu Thr Pro Glu Arg Ala      50 55 60 Gly Leu Asp Ser Ser Gln Gly Met  65 70       <210> 474 <211> 10 <212> PRT <213> Homo sapiens    <400> 474 Pro Leu Gly Pro Gly Leu Ser Arg His Ser   1 5 10       <210> 475 <211> 5 <212> PRT <213> Homo sapiens    <400> 475 Pro Leu Cys Ser Pro   1 5       <210> 476 <211> 22 <212> PRT <213> Homo sapiens    <400> 476 Ser Pro Leu Pro Thr Leu Arg Leu Leu Gly Gly Thr Met Leu Pro Thr   1 5 10 15 Leu Gly Pro Ala Pro Ala              20       <210> 477 <211> 16 <212> PRT <213> Homo sapiens    <400> 477 Gln Ser Pro Ser Ser Gln Gln Pro Gly Glu Ala Leu His Arg Val Thr   1 5 10 15       <210> 478 <211> 16 <212> PRT <213> Homo sapiens    <400> 478 Asp Gln Val Gln Glu Thr Cys Ser Ser Ile Ser Val Ser Leu Thr Ala   1 5 10 15       <210> 479 <211> 19 <212> PRT <213> Homo sapiens    <400> 479 Ser Leu Leu Gly Cys Arg Val Val Pro Thr Thr Thr Ala Lys Lys Lys   1 5 10 15 Lys Lys Lys       <210> 480 <211> 45 <212> PRT <213> Homo sapiens    <400> 480 Glu Pro Ser Thr Gly Arg Val Gly Phe Ala Ala Glu Gln Ala Ala Pro   1 5 10 15 Ser Trp Gly Leu Ala Ala Arg Arg Pro Ala Gln Tyr Cys Lys Ile Asp              20 25 30 Val Lys Gly Met Val Phe Thr Pro Leu His Gln Arg Thr          35 40 45       <210> 481 <211> 85 <212> PRT <213> Homo sapiens    <400> 481 Val Ile Ser Ser Phe Gly Pro Leu Phe Tyr Ala Ile Met Tyr Val Ile   1 5 10 15 Glu Ser Ala Arg Gln Arg Pro Pro Lys Arg Lys Tyr Leu Ser Ser Gly              20 25 30 Arg Lys Ser Val Phe Gln Lys Leu Tyr Asp Leu Tyr Ile Glu Glu Cys          35 40 45 Glu Lys Glu Pro Glu Val Lys Ile Pro Arg Pro Phe Asp Cys Pro Met      50 55 60 Lys Lys Glu Ser Cys Leu Asn Ile Trp Met Gln Lys Asn Tyr Leu Leu  65 70 75 80 Phe Trp Leu Ile Ser                  85       <210> 482 <211> 13 <212> PRT <213> Homo sapiens    <400> 482 Lys Asn Leu Arg Leu Ile Phe Phe Ile Ala Asp Val Ser   1 5 10       <210> 483 <211> 11 <212> PRT <213> Homo sapiens    <400> 483 Gln Lys Tyr Val Thr Thr Gly Ser Pro Val Thr   1 5 10       <210> 484 <211> 18 <212> PRT <213> Homo sapiens    <400> 484 Asn Leu Leu Val Thr Lys Val Gly Thr Phe Ser Tyr Val Gln Gln Cys   1 5 10 15 Arg Leu       <210> 485 <211> 6 <212> PRT <213> Homo sapiens    <400> 485 Phe Val Met Tyr Ile Gln   1 5       <210> 486 <211> 29 <212> PRT <213> Homo sapiens    <400> 486 Gln Val Ile Thr Thr Asn Gly Pro Arg Leu Val Val Leu Phe Phe Asn   1 5 10 15 Leu Lys Gln Ala Lys Tyr Arg Met Lys Lys Asn Tyr His              20 25       <210> 487 <211> 12 <212> PRT <213> Homo sapiens    <400> 487 Ala Lys Val Ile Phe Cys Leu Phe Leu Phe Asn Asn   1 5 10       <210> 488 <211> 6 <212> PRT <213> Homo sapiens    <400> 488 Lys Ala Gly Ile Pro Leu   1 5       <210> 489 <211> 17 <212> PRT <213> Homo sapiens    <400> 489 Asp Leu Glu Val Lys Gly Leu Phe Ile Cys Val Val Ile Pro Gln Val   1 5 10 15 Ala       <210> 490 <211> 8 <212> PRT <213> Homo sapiens    <400> 490 Asp His Phe Lys Val Lys Leu Ala   1 5       <210> 491 <211> 34 <212> PRT <213> Homo sapiens    <400> 491 Phe Phe Ile Ser Ser Gln Thr Glu Glu Lys Cys Phe Val Phe Thr Met   1 5 10 15 Val Thr Asn Arg Tyr Trp Phe Phe Phe Phe Gln Ile Ile Gln Val Ser              20 25 30 Lys Pro       <210> 492 <211> 26 <212> PRT <213> Homo sapiens    <400> 492 Pro Ser Leu Ser Phe Phe Ala Ile Tyr Thr Gly Cys Leu Glu Met Arg   1 5 10 15 Gly Thr Leu Leu Pro Leu Arg Ile Thr Ser              20 25       <210> 493 <211> 9 <212> PRT <213> Homo sapiens    <400> 493 Pro Leu Gln Phe Trp Leu Ser Val Ile   1 5       <210> 494 <211> 11 <212> PRT <213> Homo sapiens    <400> 494 Gly Asp Phe Arg Lys Phe Val Glu Asn Trp Asn   1 5 10       <210> 495 <211> 23 <212> PRT <213> Homo sapiens    <400> 495 Lys Ile Ile Ile Lys Asn Ile Asn Phe Ser Ser Gln Tyr Lys Leu His   1 5 10 15 Gln Val Gln Asp Ala Cys Lys              20       <210> 496 <211> 5 <212> PRT <213> Homo sapiens    <400> 496 Tyr Gln Pro Phe Ile   1 5       <210> 497 <211> 23 <212> PRT <213> Homo sapiens    <400> 497 Ser Thr Pro Glu Glu Leu Arg Val Leu Gly Thr Glu Pro Tyr Gln Cys   1 5 10 15 Asn Leu Phe Tyr Ile Ile Asn              20       <210> 498 <211> 6 <212> PRT <213> Homo sapiens    <400> 498 Arg Lys Met Gly Thr Phe   1 5       <210> 499 <211> 17 <212> PRT <213> Homo sapiens    <400> 499 Glu Thr Lys Arg Ser Gln Lys Glu Pro Asn Leu Asp Cys Lys Val His   1 5 10 15 Thr       <210> 500 <211> 18 <212> PRT <213> Homo sapiens    <400> 500 Trp Phe Pro Ile Lys Thr Leu Thr Lys Phe Leu Phe Phe Asp Glu Arg   1 5 10 15 Asn Glu       <210> 501 <211> 28 <212> PRT <213> Homo sapiens    <400> 501 Arg His Cys Gly Ala Glu Val Ser Ser Glu Ala Phe Pro Gly Ile Phe   1 5 10 15 Leu Pro Lys Leu Trp Leu Thr Phe Ser Lys His Ser              20 25       <210> 502 <211> 37 <212> PRT <213> Homo sapiens    <400> 502 Ala Arg Tyr His Ser Leu Phe Leu Gln Lys Val Asn Lys Gln Asn Val   1 5 10 15 Leu Ser Ile Pro Glu Asn Cys Phe His Asp Leu Cys Ser Ser Ser Val              20 25 30 Cys Phe Cys Phe Asp          35       <210> 503 <211> 10 <212> PRT <213> Homo sapiens    <400> 503 Ile Thr Ser Ala Ser Trp Trp Pro Leu Pro   1 5 10       <210> 504 <211> 14 <212> PRT <213> Homo sapiens    <400> 504 Leu Cys Phe Thr Ile Phe Arg Ile Ile Leu Glu Arg Met Leu   1 5 10       <210> 505 <211> 6 <212> PRT <213> Homo sapiens    <400> 505 Tyr Leu Gly Pro Thr Cys   1 5       <210> 506 <211> 28 <212> PRT <213> Homo sapiens    <400> 506 Lys Phe Leu Leu Lys Ala Leu Leu Leu Gln Leu Ile Gly Met Gln Trp   1 5 10 15 Phe Trp Tyr Pro Ser Ser Gly Lys Phe Thr Gln Leu              20 25       <210> 507 <211> 8 <212> PRT <213> Homo sapiens    <400> 507 Phe Phe Ser Gln Asn Cys Ser Gly   1 5       <210> 508 <211> 11 <212> PRT <213> Homo sapiens    <400> 508 Glu Ala Tyr Ser Val Gly Asn Cys Phe Cys Cys   1 5 10       <210> 509 <211> 6 <212> PRT <213> Homo sapiens    <400> 509 Ser Leu Val Leu Phe Ser   1 5       <210> 510 <211> 30 <212> PRT <213> Homo sapiens    <400> 510 Val Thr Asn Lys Met Asn Phe Phe Pro Arg Lys Leu Met Trp Lys Ile   1 5 10 15 Cys Cys Cys Arg Leu Arg Leu Gln His Ser Leu Val Pro Ser              20 25 30       <210> 511 <211> 24 <212> PRT <213> Homo sapiens    <400> 511 Asn Lys Leu Pro Ile Cys Lys Leu Leu Leu Ser Leu Arg His Ser Ser   1 5 10 15 His Lys Leu Phe Lys Lys His Gln              20       <210> 512 <211> 12 <212> PRT <213> Homo sapiens    <400> 512 Phe His Asn Ser Ser Thr Gln Ala Ser Pro Ser Ile   1 5 10       <210> 513 <211> 7 <212> PRT <213> Homo sapiens    <400> 513 Cys Leu Phe Leu Leu Gln Phe   1 5       <210> 514 <211> 30 <212> PRT <213> Homo sapiens    <400> 514 Gln Asn Ser Cys Cys Ser Gly Lys Gly Cys Phe Gln Thr Asp Val Leu   1 5 10 15 Ser Phe Leu Val Phe Gln Thr Arg Phe Cys Ser Asp Met Leu              20 25 30       <210> 515 <211> 12 <212> PRT <213> Homo sapiens    <400> 515 Gln Leu Ser Thr Cys Leu Phe Trp Cys Lys Lys Phe   1 5 10       <210> 516 <211> 7 <212> PRT <213> Homo sapiens    <400> 516 Asn Leu Cys Ile Val Phe Ser   1 5       <210> 517 <211> 13 <212> PRT <213> Homo sapiens    <400> 517 Tyr Ser Phe Phe Ile Asn Phe Leu Lys Thr Pro Cys Ile   1 5 10       <210> 518 <211> 18 <212> PRT <213> Homo sapiens    <400> 518 Asp Val His Phe Thr Lys Val Phe Ser Cys Leu Thr Ile Val Arg Asn   1 5 10 15 Asn Tyr       <210> 519 <211> 6 <212> PRT <213> Homo sapiens    <400> 519 Val Lys Arg Lys Tyr Gln   1 5       <210> 520 <211> 5 <212> PRT <213> Homo sapiens    <400> 520 His Val Ile Ile Asn   1 5       <210> 521 <211> 5 <212> PRT <213> Homo sapiens    <400> 521 Ala Ser Val His Gln   1 5       <210> 522 <211> 10 <212> PRT <213> Homo sapiens    <400> 522 Leu Pro Ser Ile Val Phe Trp Phe Gly Leu   1 5 10       <210> 523 <211> 7 <212> PRT <213> Homo sapiens    <400> 523 Cys Cys His Leu Gln Lys Asp   1 5       <210> 524 <211> 43 <212> PRT <213> Homo sapiens    <400> 524 Lys Leu Leu Lys Glu Tyr Trp Lys Thr Glu Lys Leu Ile Gly Tyr His   1 5 10 15 Gln Ser Leu Leu Gly His Gln Ile Leu Thr Leu Lys Ile Asp Lys Gly              20 25 30 Glu Asn Ile Ile Phe Ile Leu Pro Phe Leu Leu          35 40       <210> 525 <211> 5 <212> PRT <213> Homo sapiens    <400> 525 Leu Arg Glu Asn Ser   1 5       <210> 526 <211> 14 <212> PRT <213> Homo sapiens    <400> 526 Glu Asn Phe Gln Leu Ile Gly Ala Lys Glu Met Ile Asp Phe   1 5 10       <210> 527 <211> 16 <212> PRT <213> Homo sapiens    <400> 527 Ser Ser Glu Ser Arg Gln Gln Tyr Phe Leu Asp Val Lys Thr Ile Arg   1 5 10 15       <210> 528 <211> 10 <212> PRT <213> Homo sapiens    <400> 528 Val Asn Gly Lys Phe Tyr Asn Val Glu Ile   1 5 10       <210> 529 <211> 41 <212> PRT <213> Homo sapiens    <400> 529 Ser Asn Pro Leu Ile Glu Asp Glu Thr Val Asn Tyr Cys Val Pro Pro   1 5 10 15 Gly Leu Met Gln Glu Thr Val His Asn Ser Ser Asn Ser Thr Asn Lys              20 25 30 Glu Leu Leu Ser Lys Lys Lys Lys Lys          35 40       <210> 530 <211> 19 <212> PRT <213> Homo sapiens    <400> 530 Ser Leu Arg Arg Gly Gly Trp Ala Leu Leu Pro Ser Arg Arg Arg Arg   1 5 10 15 Leu Gly Ala       <210> 531 <211> 37 <212> PRT <213> Homo sapiens    <400> 531 Arg Arg Gly Asp Pro His Ser Thr Val Arg Leu Met Leu Lys Ala Trp   1 5 10 15 Cys Ser Pro His Phe Ile Ser Val His Lys Leu Ser Leu Leu Leu Asp              20 25 30 Pro Tyr Phe Met Pro          35       <210> 532 <211> 51 <212> PRT <213> Homo sapiens    <400> 532 Cys Met Ser Leu Lys Val Pro Asp Arg Asp Leu Leu Lys Gly Asn Thr   1 5 10 15 Tyr Gln Val Glu Glu Asn Leu Tyr Phe Lys Asn Phe Met Thr Cys Ile              20 25 30 Leu Lys Asn Val Lys Lys Asn Leu Lys Leu Arg Phe Arg Asp His Ser          35 40 45 Thr Ala Leu      50       <210> 533 <211> 5 <212> PRT <213> Homo sapiens    <400> 533 Arg Arg Arg Val Ala   1 5       <210> 534 <211> 12 <212> PRT <213> Homo sapiens    <400> 534 Ile Phe Gly Cys Arg Arg Ile Thr Ser Tyr Phe Gly   1 5 10       <210> 535 <211> 7 <212> PRT <213> Homo sapiens    <400> 535 Ser Pro Arg Lys Ile Ser Gly   1 5       <210> 536 <211> 12 <212> PRT <213> Homo sapiens    <400> 536 Tyr Phe Ser Leu Arg Met Cys His Ser Arg Asn Thr   1 5 10       <210> 537 <211> 5 <212> PRT <213> Homo sapiens    <400> 537 Leu Gln Ala Val Gln   1 5       <210> 538 <211> 22 <212> PRT <213> Homo sapiens    <400> 538 His Glu Ile Ser Trp Leu Pro Lys Ser Ala His Ser Leu Thr Ser Asn   1 5 10 15 Asn Ala Asp Phe Asn Leu              20       <210> 539 <211> 6 <212> PRT <213> Homo sapiens    <400> 539 Cys Thr Phe Asn Asn Lys   1 5       <210> 540 <211> 6 <212> PRT <213> Homo sapiens    <400> 540 Pro Gln Met Asp Pro Gly   1 5       <210> 541 <211> 13 <212> PRT <213> Homo sapiens    <400> 541 Leu Phe Cys Phe Leu Ile Ser Asn Arg Gln Asn Ile Gly   1 5 10       <210> 542 <211> 8 <212> PRT <213> Homo sapiens    <400> 542 Lys Lys Ile Ile Ile Lys Gln Lys   1 5       <210> 543 <211> 24 <212> PRT <213> Homo sapiens    <400> 543 Phe Ser Ala Tyr Phe Tyr Ser Ile Ile Lys Phe Asp Ala Leu Cys Glu   1 5 10 15 Lys Leu Val Phe Leu Tyr Lys Ile              20       <210> 544 <211> 8 <212> PRT <213> Homo sapiens    <400> 544 Lys Leu Arg Val Ser Leu Tyr Val   1 5       <210> 545 <211> 50 <212> PRT <213> Homo sapiens    <400> 545 Ser Leu Lys Leu Pro Lys Ile Ile Leu Arg Ser Ser Trp Pro Asn Ile   1 5 10 15 Phe Asn Glu Ile Lys Leu Ser Ser Leu Ser Pro Leu Lys Gln Lys Lys              20 25 30 Asn Val Leu Phe Leu Pro Trp Leu Gln Ile Asp Thr Gly Phe Phe Phe          35 40 45 Phe Lys      50       <210> 546 <211> 21 <212> PRT <213> Homo sapiens    <400> 546 Phe Lys Phe Leu Asn Pro Ser Leu Ala Tyr Leu Ser Leu Pro Phe Ile   1 5 10 15 Leu Val Ala Leu Lys              20       <210> 547 <211> 6 <212> PRT <213> Homo sapiens    <400> 547 Gly Glu Leu Ser Tyr Pro   1 5       <210> 548 <211> 26 <212> PRT <213> Homo sapiens    <400> 548 Pro Val Asn Pro Ser Ser Ser Gly Ser Val Leu Tyr Glu Gly Thr Ser   1 5 10 15 Glu Ser Leu Trp Lys Thr Gly Ile Lys Arg              20 25       <210> 549 <211> 28 <212> PRT <213> Homo sapiens    <400> 549 Thr Phe Leu Leu Asn Ile Ser Ser Ile Lys Phe Lys Met Leu Val Asn   1 5 10 15 Asp Ile Asn His Leu Phe Ser Pro Pro Leu Lys Asn              20 25       <210> 550 <211> 90 <212> PRT <213> Homo sapiens    <400> 550 Gly Ser Trp Glu Leu Asn His Ile Asn Ala Ile Phe Ser Thr Leu Leu   1 5 10 15 Thr Glu Glu Lys Trp Val Leu Phe Lys Leu Phe Phe Phe Lys Ile Arg              20 25 30 Lys Gln Lys Glu Val Arg Arg Ser Gln Ile Trp Thr Val Arg Cys Ile          35 40 45 Pro Asn Gly Phe Pro Ser Lys Leu Leu Gln Asn Phe Ser Phe Leu Met      50 55 60 Arg Gly Met Ser Arg Gly Ile Val Val Gln Lys Ser Leu Val Lys Leu  65 70 75 80 Ser Gln Ala Phe Phe Cys Arg Ser Phe Gly                  85 90       <210> 551 <211> 24 <212> PRT <213> Homo sapiens    <400> 551 Leu Ser Gln Asn Thr His Asn Lys His Val Ile Ile Leu Cys Ser Phe   1 5 10 15 Arg Lys Ser Thr Ser Lys Met Ser              20       <210> 552 <211> 57 <212> PRT <213> Homo sapiens    <400> 552 Ala Ser Gln Lys Thr Val Ser Met Ile Phe Ala Leu His Leu Ser Ala   1 5 10 15 Phe Ala Leu Thr Glu Ser Leu Leu Pro Leu Gly Gly His Cys Leu Asn              20 25 30 Cys Ala Leu Leu Ser Ser Gly Leu Tyr Trp Lys Glu Cys Phe Ser Ile          35 40 45 Leu Val Leu Leu Val Glu Asn Phe Tyr      50 55       <210> 553 <211> 6 <212> PRT <213> Homo sapiens    <400> 553 Lys Leu Cys Phe Cys Ser   1 5       <210> 554 <211> 53 <212> PRT <213> Homo sapiens    <400> 554 Ser Gly Cys Ser Gly Phe Gly Thr His Arg Val Glu Ser Leu Leu Asn   1 5 10 15 Phe Asn Phe Ser Val Lys Ile Val Gln Ala Glu Pro Val Glu Arg Pro              20 25 30 Ile Val Leu Ala Ile Val Ser Ala Val Asn His Trp Ser Ser Ser Val          35 40 45 Arg Leu Gln Thr Lys      50       <210> 555 <211> 6 <212> PRT <213> Homo sapiens    <400> 555 Ile Phe Phe Leu Val Asn   1 5       <210> 556 <211> 30 <212> PRT <213> Homo sapiens    <400> 556 Cys Gly Arg Ser Ala Ala Ala Gly Phe Val Phe Asn Ile Val Leu Ser   1 5 10 15 Leu Leu Lys Thr Ser Tyr Pro Phe Val Asn Cys Cys Phe Leu              20 25 30       <210> 557 <211> 52 <212> PRT <213> Homo sapiens    <400> 557 Gly Ile Leu Leu Ile Asn Phe Ser Lys Ser Ile Ser Asp Phe Thr Ile   1 5 10 15 Leu Pro Leu Lys Leu His His Gln Phe Asp Val Cys Ser Cys Phe Ser              20 25 30 Phe Ser Arg Ile Pro Val Ala Leu Val Lys Ala Val Phe Lys Leu Met          35 40 45 Ser Tyr Pro Ser      50       <210> 558 <211> 28 <212> PRT <213> Homo sapiens    <400> 558 Cys Phe Lys Leu Gly Ser Val Gln Thr Cys Tyr Asn Ser Leu Val His   1 5 10 15 Val Tyr Phe Gly Ala Lys Ser Phe Glu Thr Tyr Val              20 25       <210> 559 <211> 8 <212> PRT <213> Homo sapiens    <400> 559 Phe Phe Leu Asn Thr His Phe Ser   1 5       <210> 560 <211> 16 <212> PRT <213> Homo sapiens    <400> 560 Arg Pro Leu Val Tyr Glu Met Ser Thr Ser Gln Lys Cys Ser Val Ala   1 5 10 15       <210> 561 <211> 20 <212> PRT <213> Homo sapiens    <400> 561 Gly Ile Ile Thr Lys Ser Lys Glu Asn Ile Ser Asn Gly Ser Tyr Pro   1 5 10 15 Phe Cys Asp Met              20       <210> 562 <211> 29 <212> PRT <213> Homo sapiens    <400> 562 Thr Lys Leu Gln Phe Ile Ser Asn Tyr Gln Val Leu Cys Phe Gly Leu   1 5 10 15 Gly Tyr Asn Val Val Ile Tyr Lys Lys Ile Lys Ser Tyr              20 25       <210> 563 <211> 16 <212> PRT <213> Homo sapiens    <400> 563 Lys Asn Ile Gly Lys Gln Lys Asn Ser Leu Val Thr Ile Arg Val Cys   1 5 10 15       <210> 564 <211> 6 <212> PRT <213> Homo sapiens    <400> 564 Gly Ile Arg Phe Leu Leu   1 5       <210> 565 <211> 7 <212> PRT <213> Homo sapiens    <400> 565 Arg Leu Ile Lys Glu Arg Ile   1 5       <210> 566 <211> 17 <212> PRT <213> Homo sapiens    <400> 566 Tyr Leu Ser Cys Pro Ser Cys Tyr Glu Leu Tyr Phe Arg Gln Pro Ser   1 5 10 15 Asn       <210> 567 <211> 9 <212> PRT <213> Homo sapiens    <400> 567 Gly Lys Ile Leu Arg Lys Ile Ser Ser   1 5       <210> 568 <211> 18 <212> PRT <213> Homo sapiens    <400> 568 Lys Phe Glu Ser Leu Asn Glu Val Val Asn Leu Asp Ser Ser Ile Ser   1 5 10 15 Trp Met       <210> 569 <211> 13 <212> PRT <213> Homo sapiens    <400> 569 Lys Pro Leu Asp Asp Arg Leu Met Gly Asn Phe Ile Met   1 5 10       <210> 570 <211> 6 <212> PRT <213> Homo sapiens    <400> 570 Lys Ser Asp Gln Thr His   1 5       <210> 571 <211> 13 <212> PRT <213> Homo sapiens    <400> 571 Leu Lys Met Arg Gln Ser Ile Ile Val Tyr Leu Leu Val   1 5 10       <210> 572 <211> 22 <212> PRT <213> Homo sapiens    <400> 572 Cys Lys Arg Gln Tyr Thr Thr Val Val Ile Ala Pro Ile Lys Asn Ser   1 5 10 15 Cys Pro Lys Lys Lys Lys              20       <210> 573 <211> 28 <212> PRT <213> Homo sapiens    <400> 573 Ala Phe Asp Gly Ala Gly Gly Leu Cys Cys Arg Ala Gly Gly Ala Val   1 5 10 15 Leu Gly Pro Ser Gly Glu Ala Thr Arg Thr Val Leu              20 25       <210> 574 <211> 28 <212> PRT <213> Homo sapiens    <400> 574 Arg His Gly Val His Pro Thr Ser Ser Ala Tyr Ile Ser Tyr Leu Phe   1 5 10 15 Phe Trp Thr Leu Ile Leu Cys His Asn Val Cys His              20 25       <210> 575 <211> 7 <212> PRT <213> Homo sapiens    <400> 575 Lys Cys Pro Thr Glu Thr Ser   1 5       <210> 576 <211> 16 <212> PRT <213> Homo sapiens    <400> 576 Lys Glu Ile Pro Ile Lys Trp Lys Lys Ile Cys Ile Ser Lys Thr Leu   1 5 10 15       <210> 577 <211> 98 <212> PRT <213> Homo sapiens    <400> 577 Asp Ser Glu Thr Ile Arg Leu Pro Tyr Glu Glu Gly Glu Leu Leu Glu   1 5 10 15 Tyr Leu Asp Ala Glu Glu Leu Pro Pro Ile Leu Val Asp Leu Leu Glu              20 25 30 Lys Ser Gln Val Asn Ile Phe His Cys Gly Cys Val Ile Ala Glu Ile          35 40 45 Arg Asp Tyr Arg Gln Ser Ser Asn Met Lys Ser Pro Gly Tyr Gln Ser      50 55 60 Arg His Ile Leu Leu Arg Pro Thr Met Gln Thr Leu Ile Cys Asp Val  65 70 75 80 His Ser Ile Thr Ser Asp Asn His Lys Trp Thr Gln Val Ser Cys Phe                  85 90 95 Val Phe       <210> 578 <211> 6 <212> PRT <213> Homo sapiens    <400> 578 Ser Gln Thr Gly Lys Ile   1 5       <210> 579 <211> 18 <212> PRT <213> Homo sapiens    <400> 579 Asp Glu Lys Lys Leu Ser Leu Ser Lys Ser Asp Phe Leu Leu Ile Phe   1 5 10 15 Ile Gln       <210> 580 <211> 18 <212> PRT <213> Homo sapiens    <400> 580 Leu Ser Leu Met Leu Tyr Val Lys Ser Trp Tyr Ser Phe Ile Arg Ser   1 5 10 15 Arg Ser       <210> 581 <211> 16 <212> PRT <213> Homo sapiens    <400> 581 Gly Ser Leu Tyr Met Cys Ser Asn Pro Ser Ser Cys Leu Arg Ser Phe   1 5 10 15       <210> 582 <211> 10 <212> PRT <213> Homo sapiens    <400> 582 Gly Gln Ala Gly Leu Ile Tyr Ser Met Arg   1 5 10       <210> 583 <211> 21 <212> PRT <213> Homo sapiens    <400> 583 Asn Leu Val Leu Tyr Leu Leu Ser Asn Arg Arg Lys Met Phe Cys Phe   1 5 10 15 Tyr His Gly Tyr Lys              20       <210> 584 <211> 12 <212> PRT <213> Homo sapiens    <400> 584 Ile Leu Val Phe Phe Phe Ser Asn Asn Ser Ser Phe   1 5 10       <210> 585 <211> 11 <212> PRT <213> Homo sapiens    <400> 585 Pro Ile Phe Leu Cys His Leu Tyr Trp Leu Pro   1 5 10       <210> 586 <211> 48 <212> PRT <213> Homo sapiens    <400> 586 Asn Glu Gly Asn Ser Leu Thr Pro Glu Asn Asn Gln Leu Thr Pro Pro   1 5 10 15 Val Leu Ala Gln Cys Tyr Met Arg Gly Leu Gln Lys Val Cys Gly Lys              20 25 30 Leu Glu Leu Lys Asp Asn Asn Lys Lys Tyr Lys Leu Phe Phe Ser Ile          35 40 45       <210> 587 <211> 8 <212> PRT <213> Homo sapiens    <400> 587 Ala Pro Ser Ser Ser Arg Cys Leu   1 5       <210> 588 <211> 10 <212> PRT <213> Homo sapiens    <400> 588 Met Ile Ser Thr Ile Tyr Leu Val His Pro   1 5 10       <210> 589 <211> 7 <212> PRT <213> Homo sapiens    <400> 589 Arg Thr Glu Gly Pro Gly Asn   1 5       <210> 590 <211> 10 <212> PRT <213> Homo sapiens    <400> 590 Thr Ile Ser Met Gln Ser Phe Leu His Tyr   1 5 10       <210> 591 <211> 28 <212> PRT <213> Homo sapiens    <400> 591 Leu Lys Lys Asn Gly Tyr Phe Leu Asn Phe Phe Phe Leu Arg Leu Gly   1 5 10 15 Asn Lys Lys Lys Ser Glu Gly Ala Lys Ser Gly Leu              20 25       <210> 592 <211> 17 <212> PRT <213> Homo sapiens    <400> 591 Gly Ala Tyr Leu Met Val Ser His Gln Asn Ser Tyr Lys Ile Ser Leu   1 5 10 15 Phe       <210> 593 <211> 9 <212> PRT <213> Homo sapiens    <400> 593 Val Glu Ala Leu Trp Cys Arg Ser Leu   1 5       <210> 594 <211> 45 <212> PRT <213> Homo sapiens    <400> 594 Ser Phe Pro Arg His Phe Ser Ala Glu Ala Leu Ala Asn Phe Leu Lys   1 5 10 15 Thr Leu Ile Ile Ser Thr Leu Ser Phe Phe Val Pro Ser Glu Ser Gln              20 25 30 Gln Ala Lys Cys Leu Glu His Pro Arg Lys Leu Phe Pro          35 40 45       <210> 595 <211> 10 <212> PRT <213> Homo sapiens    <400> 595 Ser Leu Leu Phe Ile Cys Leu Leu Leu Leu   1 5 10       <210> 596 <211> 78 <212> PRT <213> Homo sapiens    <400> 596 Leu Asn His Phe Cys Leu Leu Val Ala Ile Ala Leu Ile Val Leu Tyr   1 5 10 15 Tyr Leu Gln Asp Tyr Thr Gly Lys Asn Ala Leu Val Ser Trp Ser Tyr              20 25 30 Leu Leu Lys Ile Ser Ile Glu Ser Ser Ala Phe Ala Ala Asp Arg Asp          35 40 45 Ala Val Val Leu Val Pro Ile Glu Trp Lys Val Tyr Ser Thr Leu Ile      50 55 60 Phe Gln Ser Lys Leu Phe Arg Leu Asn Gln Leu Arg Gly Leu  65 70 75       <210> 597 <211> 25 <212> PRT <213> Homo sapiens    <400> 597 Cys Trp Gln Leu Phe Leu Leu Leu Ile Ile Gly Pro Leu Gln Leu Gly   1 5 10 15 Tyr Lys Gln Asn Glu Phe Phe Ser Ser              20 25       <210> 598 <211> 14 <212> PRT <213> Homo sapiens    <400> 598 Ile Asp Val Glu Asp Leu Leu Leu Gln Ala Ser Ser Ser Thr   1 5 10       <210> 599 <211> 11 <212> PRT <213> Homo sapiens    <400> 599 Ser Cys Pro Phe Leu Lys Gln Val Thr His Leu   1 5 10       <210> 600 <211> 10 <212> PRT <213> Homo sapiens    <400> 600 Thr Ala Ala Phe Phe Glu Ala Phe Phe Ser   1 5 10       <210> 601 <211> 35 <212> PRT <213> Homo sapiens    <400> 601 Thr Phe Gln Lys Ala Ser Val Ile Ser Gln Phe Phe His Ser Ser Phe   1 5 10 15 Thr Ile Asn Leu Met Phe Val Leu Ala Ser Val Leu Ala Glu Phe Leu              20 25 30 Leu Leu Trp          35       <210> 602 <211> 5 <212> PRT <213> Homo sapiens    <400> 602 Arg Leu Phe Ser Asn   1 5       <210> 603 <211> 9 <212> PRT <213> Homo sapiens    <400> 603 Cys Leu Ile Leu Leu Ser Val Ser Asn   1 5       <210> 604 <211> 9 <212> PRT <213> Homo sapiens    <400> 604 Val Leu Phe Arg His Val Ile Thr Ala   1 5       <210> 605 <211> 48 <212> PRT <213> Homo sapiens    <400> 605 Tyr Met Phe Ile Leu Val Gln Lys Val Leu Lys Pro Met Tyr Ser Phe   1 5 10 15 Phe Leu Ile Leu Ile Phe His Lys Leu Phe Lys Asp Pro Leu Tyr Met              20 25 30 Arg Cys Pro Leu His Lys Ser Val Gln Leu Pro Asp Tyr Ser Glu Glu          35 40 45       <210> 606 <211> 76 <212> PRT <213> Homo sapiens    <400> 606 Leu Leu Ser Gln Lys Lys Ile Ser Val Met Val Val Ile Leu Ser Val   1 5 10 15 Thr Cys Asp Tyr Lys Leu Ser Phe Ser Ser Ser Val Thr Thr Lys Tyr              20 25 30 Cys Val Leu Val Trp Ala Ile Met Leu Ser Ser Thr Lys Arg Leu Lys          35 40 45 Ala Ile Lys Arg Ile Leu Glu Asn Arg Lys Thr His Trp Leu Pro Ser      50 55 60 Glu Phe Ala Arg Ala Ser Asp Ser Tyr Ser Glu Asp  65 70 75       <210> 607 <211> 52 <212> PRT <213> Homo sapiens    <400> 607 Arg Arg Glu Tyr Asn Ile Tyr Pro Ala Leu Leu Val Met Asn Cys Ile   1 5 10 15 Leu Gly Ser Gln Val Thr Glu Gly Lys Phe Leu Gly Lys Phe Pro Ala              20 25 30 Asn Arg Cys Lys Arg Asn Asp Arg Leu Leu Lys Asn Lys Ser Leu Lys          35 40 45 Val Leu Met Lys      50       <210> 608 <211> 10 <212> PRT <213> Homo sapiens    <400> 608 Thr Ala Val Phe Leu Gly Cys Glu Asn His   1 5 10       <210> 609 <211> 9 <212> PRT <213> Homo sapiens    <400> 609 Cys Arg Asn Leu Ile Lys Pro Thr Asp   1 5       <210> 610 <211> 18 <212> PRT <213> Homo sapiens    <400> 610 Asp Ser Gln Leu Leu Cys Thr Ser Trp Phe Asp Ala Arg Asp Ser Thr   1 5 10 15 Gln Gln       <210> 611 <211> 9 <212> PRT <213> Homo sapiens    <400> 611 Arg Thr Leu Val Gln Lys Lys Lys Lys   1 5       <210> 612 <211> 118 <212> PRT <213> Homo sapiens    <400> 612 Ala Gly Phe Cys Leu Arg Pro Cys Pro Ala Leu Leu Cys Ala Leu Cys   1 5 10 15 Pro Arg Arg Arg Arg Leu Ser Leu Gly Pro Ala Leu Arg Ala Arg Pro              20 25 30 Val Leu Pro Trp Pro Ala Ala Arg Glu Ala Arg Arg Gly Ile Arg Ala          35 40 45 Ala Ala Thr Val Thr Pro Ala Arg Arg Pro Pro Arg Asp Gly Ala Trp      50 55 60 Asp Gly Ser Ala Glu Pro Thr Ala Gly Ala Gly Gly Pro Lys Thr Pro  65 70 75 80 Arg Arg Gln Ser Thr Ala Ala Pro Ser Ala Asp Pro Arg Ala Leu Pro                  85 90 95 Leu Leu Lys Ala Leu Asn Pro Val Pro Asp Ala Leu Thr Gly Gln Val             100 105 110 Gln Leu Lys Lys Met Lys         115       <210> 613 <211> 50 <212> PRT <213> Homo sapiens    <400> 613 Gly Pro Glu Leu Thr Lys Lys Trp Gln Asp Ile Lys Gly Asn Ser Ser   1 5 10 15 Ser Met Thr Leu Glu Glu Arg Glu Asn His His Gln Glu Val Leu Ile              20 25 30 Gln Arg Ser Leu Cys Leu Leu Cys Arg Leu Thr Leu Arg Gln Met Lys          35 40 45 Val Ser      50       <210> 614 <211> 76 <212> PRT <213> Homo sapiens    <400> 614 Gly Asp Arg Ser Arg Ser Thr Met Gly Arg Thr Gln Leu Pro Thr Ile   1 5 10 15 Val Ile Leu Lys Lys Ser Gln Asp Thr Phe Asp Asn Leu Ala Phe Ile              20 25 30 Pro Arg Pro Leu Ile Asn Leu Arg Ser Ile Val Asp Val His Gly Thr          35 40 45 Ser Lys Ser Asn Ser Gly Arg Trp Leu Cys Ile Phe Gly Ile Leu Gln      50 55 60 Arg Lys Lys Asp Val Ile Cys Lys Lys Tyr Thr Leu  65 70 75       <210> 615 <211> 28 <212> PRT <213> Homo sapiens    <400> 615 Thr Leu Asn Leu Gln Lys Ala Ala Pro Ser Pro Arg Pro Ala Leu Arg   1 5 10 15 Met Thr Leu Met Cys Thr Leu Ala His Pro Pro Arg              20 25       <210> 616 <211> 16 <212> PRT <213> Homo sapiens    <400> 616 Asp Thr Trp Thr Val Lys Trp Arg Met Ser Leu Ile Trp Lys Leu Val   1 5 10 15       <210> 617 <211> 5 <212> PRT <213> Homo sapiens    <400> 617 Glu Thr Ser Gln Pro   1 5       <210> 618 <211> 40 <212> PRT <213> Homo sapiens    <400> 618 Ala Asn Cys Pro Leu Ala Ala Arg Lys Arg Asn Ser Ser Ser Pro Thr   1 5 10 15 Arg Trp Lys Ala Gly Gln Ala Pro Ser Met Cys Val His Leu Tyr Leu              20 25 30 Val Val Ser Leu Leu Ala Val His          35 40       <210> 619 <211> 31 <212> PRT <213> Homo sapiens    <400> 619 Leu Met Leu Asn Tyr Phe Cys Leu Thr Phe Leu Arg Asn Ile Asn Phe   1 5 10 15 Met Tyr Ser Glu Tyr Ile Leu His Val Leu Asn Cys Lys Trp Ser              20 25 30       <210> 620 <211> 5 <212> PRT <213> Homo sapiens    <400> 620 Val Gln Glu Ser Thr   1 5       <210> 621 <211> 9 <212> PRT <213> Homo sapiens    <400> 621 Ser Ser Leu Pro Ala Ser Leu Ile Ala   1 5       <210> 622 <211> 8 <212> PRT <213> Homo sapiens    <400> 622 Ser Leu Leu Ser Ser Arg Val Ser   1 5       <210> 623 <211> 31 <212> PRT <213> Homo sapiens    <400> 623 His Val Tyr Ile Thr Gly Phe Pro Gln Ala Ser Ser Val Ile Ala Cys   1 5 10 15 Gln Val Asp Cys Phe Gly Phe Asn His Val Ile His Gly Thr Asn              20 25 30       <210> 624 <211> 21 <212> PRT <213> Homo sapiens    <400> 624 Glu Ser Ala Thr Phe Ile Gly Ile Lys Val Phe Ser Asp Thr Phe Asn   1 5 10 15 Ile Phe Met Glu Thr              20       <210> 625 <211> 12 <212> PRT <213> Homo sapiens    <400> 625 Phe Leu Ala Phe Tyr Gln Tyr Val Ile Thr Ala Phe   1 5 10       <210> 626 <211> 6 <212> PRT <213> Homo sapiens    <400> 626 Ser Gln Thr Leu Leu Asn   1 5       <210> 627 <211> 8 <212> PRT <213> Homo sapiens    <400> 627 Ala Ile Lys Leu Met Ser Phe Met   1 5          <210> 628 <211> 5 <212> PRT <213> Homo sapiens    <400> 628 Phe Gly Thr Cys Lys   1 5          <210> 629 <211> 9 <212> PRT <213> Homo sapiens    <400> 629 Leu Asp Ser Leu Glu Tyr Ser Lys Ser   1 5       <210> 630 <211> 57 <212> PRT <213> Homo sapiens    <400> 630 Gly Ser Arg Val Glu Arg Phe Arg Lys Asn Ile Leu Lys Gln Ser Val   1 5 10 15 Asn Leu Pro Cys Lys Ile Ala Val Asn Asp Asn Val Tyr Arg Phe Ser              20 25 30 Val Gln Ile Phe Asn Cys Lys Leu Leu Val Lys Thr Val Thr Phe Leu          35 40 45 Leu Leu Leu Tyr Gly Ile Leu Gln Lys      50 55       <210> 631 <211> 6 <212> PRT <213> Homo sapiens    <400> 631 Lys Gly Lys Asn Pro Leu   1 5       <210> 632 <211> 51 <212> PRT <213> Homo sapiens    <400> 632 Arg Val Ser Ala Ser Gly Pro Ala Leu Leu Tyr Ser Ala Leu Ser Ala   1 5 10 15 Arg Ala Ala Ala Ala Ser Ala Ser Ala Leu Arg Cys Ala Pro Gly Pro              20 25 30 Cys Cys His Gly Leu Pro Pro Ala Lys Pro Ala Glu Ala Ser Glu Pro          35 40 45 Leu Arg Arg      50       <210> 633 <211> 45 <212> PRT <213> Homo sapiens    <400> 633 Arg Gln Pro Ala Val Pro Arg Ala Met Glu Pro Gly Thr Glu Ala Gln   1 5 10 15 Ser Arg Arg Gln Ala Leu Glu Ala Arg Arg Arg Arg Gly Gly Arg Ala              20 25 30 Pro Arg Arg Arg Ala Gln Thr Arg Glu Leu Tyr His Ser          35 40 45          <210> 634 <211> 6 <212> PRT <213> Homo sapiens    <400> 634 Thr Pro Phe Gln Met Leu   1 5       <210> 635 <211> 5 <212> PRT <213> Homo sapiens    <400> 635 Leu Gly Lys Cys Ser   1 5       <210> 636 <211> 5 <212> PRT <213> Homo sapiens    <400> 636 Asn Glu Asp Gln Ser   1 5       <210> 637 <211> 6 <212> PRT <213> Homo sapiens    <400> 637 Gln Arg Asn Gly Lys Ile   1 5       <210> 638 <211> 6 <212> PRT <213> Homo sapiens    <400> 638 Lys Glu Thr Pro His Gln   1 5       <210> 639 <211> 12 <212> PRT <213> Homo sapiens    <400> 639 Leu Trp Lys Arg Glu Lys Ile Ile Ile Arg Lys Phe   1 5 10       <210> 640 <211> 10 <212> PRT <213> Homo sapiens    <400> 640 Phe Lys Gly Val Tyr Val Tyr Cys Ala Gly   1 5 10       <210> 641 <211> 23 <212> PRT <213> Homo sapiens    <400> 641 Lys Cys Pro Asn Glu Glu Thr Glu Ala Asp Gln Leu Trp Glu Glu His   1 5 10 15 Asn Cys Leu Arg Ser Leu Tyr              20       <210> 642 <211> 16 <212> PRT <213> Homo sapiens    <400> 642 Arg Ser Pro Lys Thr Pro Ser Thr Thr Trp His Ser Ser Gln Asp Pro   1 5 10 15       <210> 643 <211> 26 <212> PRT <213> Homo sapiens    <400> 643 Ser Thr Phe Met Gly Pro Ala Asn Gln Thr Leu Glu Gly Gly Ser Ala   1 5 10 15 Phe Leu Gly Ser Ser Ser Gly Arg Arg Met              20 25       <210> 644 <211> 9 <212> PRT <213> Homo sapiens    <400> 644 Phe Ala Arg Asn Thr Pro Cys Arg Pro   1 5       <210> 645 <211> 14 <212> PRT <213> Homo sapiens    <400> 645 Ile Cys Arg Lys Gln Leu Arg Ala Pro Asp Gln Leu Ser Gly   1 5 10       <210> 646 <211> 18 <212> PRT <213> Homo sapiens    <400> 646 Cys Val Leu Trp His Thr His Gln Gly Glu Thr His Gly Gln Ser Ser   1 5 10 15 Gly Gly       <210> 647 <211> 6 <212> PRT <213> Homo sapiens    <400> 647 Phe Gly Ser Leu Phe Asn   1 5       <210> 648 <211> 45 <212> PRT <213> Homo sapiens    <400> 648 Thr Leu Glu Arg Leu Leu Ser His Glu Leu Thr Ala Pro Trp Arg Pro   1 5 10 15 Gly Arg Glu Thr Ala Pro Pro Arg Leu Gly Gly Arg Leu Ala Arg His              20 25 30 Gln Ala Cys Val Cys Thr Cys Thr Trp Trp Phe Leu Cys          35 40 45       <210> 649 <211> 6 <212> PRT <213> Homo sapiens    <400> 649 Gln Ser Ile Ser Ser Cys   1 5       <210> 650 <211> 7 <212> PRT <213> Homo sapiens    <400> 650 Ile Ile Phe Ala Leu Leu Ser   1 5       <210> 651 <211> 14 <212> PRT <213> Homo sapiens    <400> 651 Glu Thr Leu Ile Leu Cys Ile Val Ser Ile Phe Cys Met Phe   1 5 10       <210> 652 <211> 18 <212> PRT <213> Homo sapiens    <400> 652 Ile Val Asn Gly Ala Lys Ser Lys Lys Val Leu Glu Ala Leu Phe Gln   1 5 10 15 Arg Ala       <210> 653 <211> 9 <212> PRT <213> Homo sapiens    <400> 653 Leu Arg Asn Pro Cys Cys Pro Pro Gly   1 5       <210> 654 <211> 5 <212> PRT <213> Homo sapiens    <400> 654 Ala Asp Thr Ser Thr   1 5       <210> 655 <211> 21 <212> PRT <213> Homo sapiens    <400> 655 Leu Val Phe His Arg His Leu Gln Leu Leu Leu Val Arg Trp Thr Val   1 5 10 15 Leu Asp Leu Thr Met              20       <210> 656 <211> 11 <212> PRT <213> Homo sapiens    <400> 656 Ser Met Gly Pro Ile Glu Ser Gln Leu Leu Leu   1 5 10       <210> 657 <211> 24 <212> PRT <213> Homo sapiens    <400> 657 Ala Ser Lys Tyr Ser Gln Thr Pro Leu Ile Ser Leu Trp Lys Leu Asn   1 5 10 15 Phe Trp Pro Phe Ile Asn Met Ser              20       <210> 658 <211> 8 <212> PRT <213> Homo sapiens    <400> 658 Gln His Ser Glu Val Arg His Cys   1 5       <210> 659 <211> 5 <212> PRT <213> Homo sapiens    <400> 659 Ile Glu Leu Leu Asn   1 5       <210> 660 <211> 17 <212> PRT <213> Homo sapiens    <400> 660 Val Leu Cys Lys Leu Tyr Gly Leu Asn Leu Val Leu Val Asn Ser Thr   1 5 10 15 Ser       <210> 661 <211> 17 <212> PRT <213> Homo sapiens    <400> 661 Asn Thr Pro Arg Val Arg Ala Ala Glu Trp Ser Asp Leu Glu Arg Thr   1 5 10 15 Phe       <210> 662 <211> 11 <212> PRT <213> Homo sapiens    <400> 662 Asn Asn Gln Leu Ile Tyr His Val Lys Leu Leu   1 5 10       <210> 663 <211> 39 <212> PRT <213> Homo sapiens    <400> 663 Met Ile Met Cys Thr Asp Phe Leu Phe Lys Tyr Ser Ile Val Asn Phe   1 5 10 15 Leu Leu Arg Leu Leu Arg Phe Tyr Cys Phe Cys Met Gly Tyr Cys Lys              20 25 30 Asn Lys Lys Glu Arg Thr Leu          35       <210> 664 <211> 304 <212> PRT <213> Homo sapiens    <400> 664 Gly Phe Leu Pro Gln Ala Leu Pro Cys Ser Thr Leu Arg Ser Leu Pro   1 5 10 15 Ala Pro Pro Pro Pro Gln Pro Arg Pro Cys Ala Ala Arg Pro Ala Arg              20 25 30 Ala Ala Met Ala Cys Arg Pro Arg Ser Pro Pro Arg His Gln Ser Arg          35 40 45 Cys Asp Gly Asp Ala Ser Pro Pro Ser Pro Ala Arg Trp Ser Leu Gly      50 55 60 Arg Lys Arg Arg Ala Asp Gly Arg Arg Trp Arg Pro Glu Asp Ala Glu  65 70 75 80 Glu Ala Glu His Arg Gly Ala Glu Arg Arg Pro Glu Ser Phe Thr Thr                  85 90 95 Pro Glu Gly Pro Lys Pro Arg Ser Arg Cys Ser Asp Trp Ala Ser Ala             100 105 110 Val Glu Glu Asp Glu Met Arg Thr Arg Val Asn Lys Glu Met Ala Arg         115 120 125 Tyr Lys Arg Lys Leu Leu Ile Asn Asp Phe Gly Arg Glu Arg Lys Ser     130 135 140 Ser Ser Gly Ser Ser Asp Ser Lys Glu Ser Met Ser Thr Val Pro Ala 145 150 155 160 Asp Phe Glu Thr Asp Glu Ser Val Leu Met Arg Arg Gln Lys Gln Ile                 165 170 175 Asn Tyr Gly Lys Asn Thr Ile Ala Tyr Asp Arg Tyr Ile Lys Glu Val             180 185 190 Pro Arg His Leu Arg Gln Pro Gly Ile His Pro Lys Thr Pro Asn Lys         195 200 205 Phe Lys Lys Tyr Ser Arg Arg Ser Trp Asp Gln Gln Ile Lys Leu Trp     210 215 220 Lys Val Ala Leu His Phe Trp Asp Pro Pro Ala Glu Glu Gly Cys Asp 225 230 235 240 Leu Gln Glu Ile His Pro Val Asp Leu Glu Ser Ala Glu Ser Ser Ser                 245 250 255 Glu Pro Gln Thr Ser Ser Gln Asp Asp Phe Asp Val Tyr Ser Gly Thr             260 265 270 Pro Thr Lys Val Arg His Met Asp Ser Gln Val Glu Asp Glu Phe Asp         275 280 285 Leu Glu Ala Cys Leu Thr Glu Pro Leu Arg Asp Phe Ser Ala Met Ser     290 295 300       <210> 665 <211> 14 <212> PRT <213> Homo sapiens    <400> 665 Leu Pro Pro Gly Gly Gln Glu Glu Lys Gln Leu Leu Pro Asp   1 5 10       <210> 666 <211> 38 <212> PRT <213> Homo sapiens    <400> 666 Val Glu Gly Trp Pro Gly Thr Lys His Val Cys Ala Leu Val Pro Gly   1 5 10 15 Gly Phe Ser Val Ser Ser Pro Leu Ala His Ala Glu Leu Phe Leu Pro              20 25 30 Tyr Phe Leu Lys Lys His          35       <210> 667 <211> 8 <212> PRT <213> Homo sapiens    <400> 667 Val Tyr Phe Ala Cys Phe Lys Leu   1 5       <210> 668 <211> 51 <212> PRT <213> Homo sapiens    <400> 668 Met Glu Leu Ser Pro Arg Lys Tyr Leu Lys Leu Ser Ser Ser Glu Leu   1 5 10 15 Asn Cys Val Ile Pro Val Val Leu Gln Gly Lys Leu Thr Arg Leu His              20 25 30 Asn Trp Phe Ser Thr Gly Ile Phe Ser Tyr Cys Leu Ser Gly Gly Leu          35 40 45 Phe Trp Ile      50       <210> 669 <211> 23 <212> PRT <213> Homo sapiens    <400> 669 Pro Cys Asn Pro Trp Asp Gln Leu Arg Val Ser Tyr Phe Tyr Arg His   1 5 10 15 Gln Ser Ile Leu Arg His Leu              20       <210> 670 <211> 28 <212> PRT <213> Homo sapiens    <400> 670 Tyr Leu Tyr Gly Asn Leu Ile Phe Gly Leu Leu Ser Ile Cys His Asn   1 5 10 15 Ser Ile Leu Lys Ser Asp Ile Val Lys Leu Ser Tyr              20 25       <210> 671 <211> 15 <212> PRT <213> Homo sapiens    <400> 671 Thr Asn Glu Phe Tyr Val Ser Tyr Met Val Leu Ile Trp Tyr Leu   1 5 10 15       <210> 672 <211> 20 <212> PRT <213> Homo sapiens    <400> 672 Ile Ala Leu Val Arg Leu Phe Arg Ile Leu Gln Glu Leu Gly Gln Gln   1 5 10 15 Ser Gly Ala Ile              20       <210> 673 <211> 8 <212> PRT <213> Homo sapiens    <400> 673 Lys Glu His Phe Lys Thr Ile Ser   1 5       <210> 674 <211> 11 <212> PRT <213> Homo sapiens    <400> 674 Cys Val Gln Ile Phe Cys Ser Asn Ile Gln Leu   1 5 10       <210> 675 <211> 21 <212> PRT <213> Homo sapiens    <400> 675 Asp Cys Tyr Val Ser Ile Ala Phe Val Trp Asp Ile Ala Lys Ile Lys   1 5 10 15 Arg Lys Glu Pro Ser              20       <210> 676 <211> 42 <212> PRT <213> Homo sapiens    <400> 676 Arg Ser Phe Tyr Lys Ile Arg Glu Ala Ser Ser Met Val Ile Gly Arg   1 5 10 15 Asn Phe Ser Asp Leu Asn Gln Val Leu Met Leu Lys Trp Lys Ile Leu              20 25 30 Phe Lys Ala Cys Ile Phe Lys Glu Tyr Leu          35 40       <210> 677 <211> 143 <212> PRT <213> Homo sapiens    <400> 677 Thr Phe Leu Ser Gly Ile Phe Leu Phe Leu Leu Asn Thr Ser Phe Phe   1 5 10 15 Asp Leu Lys Met Leu Ala Ser Glu Cys Leu Thr Asn Leu Cys Phe Cys              20 25 30 Pro Phe Gln Leu Ser Leu Ser Pro Val His Gln Phe Leu Ser Pro Val          35 40 45 Leu Leu Arg Val Lys Lys Lys Leu Leu Asn Cys Pro Asn Gln Arg Lys      50 55 60 Thr Asp Val Ser Cys Ala Glu Arg Lys Leu Val Leu Gln Gly Leu Thr  65 70 75 80 Ala Asp Val Glu Ile Cys Phe Val Asp Phe Thr Val Thr Leu Thr Ser                  85 90 95 Thr Thr Val Arg Met Ile Thr Lys Gln Lys Leu Gln Gln Lys Ser Glu             100 105 110 Lys Arg Ile Gln Leu Leu Trp Leu Lys Lys Phe Arg Glu Tyr Lys Leu         115 120 125 Leu Leu Val Lys Arg Leu Lys Leu Cys Phe Tyr Phe Asn Ile Ser     130 135 140       <210> 678 <211> 27 <212> PRT <213> Homo sapiens    <400> 678 Glu Asn Ile Lys Glu Gln Met His Gly His Phe Ser Leu Met Phe Ser   1 5 10 15 Arg Val Leu His Tyr Thr Cys Leu Ser Tyr Asn              20 25       <210> 679 <211> 25 <212> PRT <213> Homo sapiens    <400> 679 Tyr Phe Arg Met Phe Gly Cys Leu Leu Gln Ala Glu Leu Asp Arg Tyr   1 5 10 15 Ser Pro Thr Asn Val Tyr Ala Leu Pro              20 25       <210> 680 <211> 20 <212> PRT <213> Homo sapiens    <400> 680 Lys Lys Leu Asp Glu Asn Leu His Ser Lys Val Lys His Thr Asp Asn   1 5 10 15 Arg Asn Lys Met              20       <210> 681 <211> 8 <212> PRT <213> Homo sapiens    <400> 681 Phe Pro Cys Ala Lys Gln Asn Lys   1 5       <210> 682 <211> 17 <212> PRT <213> Homo sapiens    <400> 682 Asn Leu Cys Met Phe Ala Ala Tyr Leu Pro Phe Gly Asn Val Ile Lys   1 5 10 15 Val       <210> 683 <211> 25 <212> PRT <213> Homo sapiens    <400> 683 Ser Leu Ala Ser Val Met Cys Leu Tyr Phe Phe Lys Met Val His Gln   1 5 10 15 Lys Arg Thr Gly Ser Leu Leu Leu Pro              20 25       <210> 684 <211> 40 <212> PRT <213> Homo sapiens    <400> 684 Leu Asn Phe Thr Leu Phe Asn Phe Thr Thr Tyr Ser Leu Glu Ala Gly   1 5 10 15 Arg Asn Ala His Lys Glu Asp Gln Thr Phe Phe Pro Val Lys Pro Val              20 25 30 Phe Gly Ala Ile Tyr Lys Pro Gly          35 40       <210> 685 <211> 14 <212> PRT <213> Homo sapiens    <400> 685 Ile Gly His Leu Lys Leu Ser Asn Lys Thr Phe Cys Glu Arg   1 5 10       <210> 686 <211> 16 <212> PRT <213> Homo sapiens    <400> 686 Thr Ser Lys Leu Val Ile Ser Lys Thr Ile Lys Pro Thr Thr Gly Ser   1 5 10 15       <210> 687 <211> 16 <212> PRT <213> Homo sapiens    <400> 687 Ser Leu Leu Tyr Trp Pro Ala Pro Glu Asp Val Cys Ile Thr His Cys   1 5 10 15       <210> 688 <211> 30 <212> PRT <213> Homo sapiens    <400> 688 Lys Cys Val Ala Gln Asn Cys Thr Arg Ile Asn Leu Phe Thr Arg Arg   1 5 10 15 Asn Leu Asn Ser Thr Phe Gly Phe His Ile Gln Gln Leu Tyr              20 25 30       <210> 689 <211> 7 <212> PRT <213> Homo sapiens    <400> 689 Ile Leu Ser Cys Lys Gly Ile   1 5       <210> 690 <211> 21 <212> PRT <213> Homo sapiens    <400> 690 Ile Ile Phe His Val His Leu Leu Ser Asn Val Leu Val Gln Glu Arg   1 5 10 15 Met Phe Lys Ala Phe              20       <210> 691 <211> 43 <212> PRT <213> Homo sapiens    <400> 691 Lys Thr Ser Val Leu Asn Val Thr Val Pro Phe Cys Met Glu Asn His   1 5 10 15 Asn Gln His Gly Cys Ser Arg Leu Leu Ser Gly Ile Gln Arg His Leu              20 25 30 Gln Arg Ala Ala Leu Ser Tyr Cys Thr Trp Val          35 40       <210> 692 <211> 21 <212> PRT <213> Homo sapiens    <400> 692 Asp Ser Ser Val Leu Gly Cys Ile Ala Trp Ala Ala Leu Ser Thr Ala   1 5 10 15 Leu Tyr Asn Asn Asn              20       <210> 693 <211> 11 <212> PRT <213> Homo sapiens    <400> 693 Lys Arg Gln Tyr Thr Ser Leu Met Leu Val Trp   1 5 10       <210> 694 <211> 20 <212> PRT <213> Homo sapiens    <400> 694 Ser Leu Leu Cys Tyr Asn Gly Arg Phe Phe Val Met Tyr Glu Thr Cys   1 5 10 15 Val Phe Tyr Ile              20       <210> 695 <211> 15 <212> PRT <213> Homo sapiens    <400> 695 Met Ser Ile Val Ser Val Val Val Met Pro Val Phe Ile Cys Lys   1 5 10 15       <210> 696 <211> 9 <212> PRT <213> Homo sapiens    <400> 696 Leu Ser Met Tyr Thr Arg His Tyr Phe   1 5       <210> 697 <211> 13 <212> PRT <213> Homo sapiens    <400> 697 Phe Ile Ala Met Phe Ser Pro Ser Phe Tyr Phe Tyr Ser   1 5 10       <210> 698 <211> 11 <212> PRT <213> Homo sapiens    <400> 698 Ser Ile Gln Phe Cys Phe Gln Phe Tyr Val Pro   1 5 10       <210> 699 <211> 8 <212> PRT <213> Homo sapiens    <400> 699 Val Arg Pro Ala Asp Val Tyr Arg   1 5       <210> 700 <211> 7 <212> PRT <213> Homo sapiens    <400> 700 Phe Ile Phe Met Tyr Cys Thr   1 5       <210> 701 <211> 12 <212> PRT <213> Homo sapiens    <400> 701 Ser Cys Tyr Ser Ala Leu Met Leu Tyr Cys Ile Met   1 5 10       <210> 702 <211> 9 <212> PRT <213> Homo sapiens    <400> 702 Ile Ile Lys Ala Met Tyr Arg Gly Lys   1 5       <210> 703 <211> 12 <212> PRT <213> Homo sapiens    <400> 703 Asp Leu Phe Thr Lys Leu Glu Lys Gln Val Val Trp   1 5 10       <210> 704 <211> 7 <212> PRT <213> Homo sapiens    <400> 704 Leu Ala Gly Ile Ser Gln Ile   1 5       <210> 705 <211> 26 <212> PRT <213> Homo sapiens    <400> 705 Asn Gly Arg Phe Cys Leu Lys Leu Val Phe Ser Arg Asn Thr Tyr Lys   1 5 10 15 His Phe Tyr Gln Ala Ser Ser Cys Phe Ser              20 25       <210> 706 <211> 6 <212> PRT <213> Homo sapiens    <400> 706 Ile Leu Pro Phe Leu Thr   1 5       <210> 707 <211> 25 <212> PRT <213> Homo sapiens    <400> 707 Gln Ile Cys Val Phe Val Leu Phe Ser Cys His Ser Ala Gln Ser Ile   1 5 10 15 Ser Phe Ser Ala Gln Tyr Phe Ser Glu              20 25       <210> 708 <211> 21 <212> PRT <213> Homo sapiens    <400> 708 Ile Ala Gln Thr Lys Glu Lys Gln Met Phe His Val Gln Lys Glu Ser   1 5 10 15 Trp Ser Tyr Arg Val              20       <210> 709 <211> 14 <212> PRT <213> Homo sapiens    <400> 709 Leu Pro Met Trp Lys Phe Val Leu Trp Thr Ser Pro Leu Leu   1 5 10       <210> 710 <211> 6 <212> PRT <213> Homo sapiens    <400> 710 Gln Ala Gln Leu Ser Val   1 5       <210> 711 <211> 18 <212> PRT <213> Homo sapiens    <400> 711 Leu Gln Ser Arg Ser Cys Ser Lys Asn Gln Lys Arg Glu Ser Ser Cys   1 5 10 15 Cys Gly       <210> 712 <211> 10 <212> PRT <213> Homo sapiens    <400> 712 Lys Asn Ser Glu Asn Ile Asn Tyr Phe Leu   1 5 10       <210> 713 <211> 22 <212> PRT <213> Homo sapiens    <400> 713 Asn Phe Val Phe Ile Leu Ile Tyr Arg Arg Lys Thr Leu Lys Ser Arg   1 5 10 15 Cys Met Ala Ile Phe Leu              20       <210> 714 <211> 51 <212> PRT <213> Homo sapiens    <400> 714 Cys Ser Pro Glu Phe Tyr Ile Thr Leu Val Cys Leu Ile Ile Asp Ile   1 5 10 15 Leu Gly Cys Leu Gly Val Cys Tyr Arg Gln Asn Trp Ile Asp Thr Ala              20 25 30 Leu Gln Met Tyr Met Pro Ser Pro Glu Lys Asn Trp Met Lys Ile Cys          35 40 45 Thr Ala Lys      50       <210> 715 <211> 32 <212> PRT <213> Homo sapiens    <400> 715 Asn Thr Gln Ile Ile Gly Thr Lys Cys Ser Ser His Val Pro Asn Lys   1 5 10 15 Ile Asn Glu Ile Ser Ala Cys Leu Gln His Ile Cys Leu Leu Gly Met              20 25 30       <210> 716 <211> 30 <212> PRT <213> Homo sapiens    <400> 716 Ser Arg Tyr Asn Leu Trp Leu Val Leu Cys Ala Cys Ile Phe Leu Lys   1 5 10 15 Trp Tyr Thr Arg Lys Gly Leu Ala Val Tyr Phe Tyr His Ser              20 25 30       <210> 717 <211> 27 <212> PRT <213> Homo sapiens    <400> 717 Thr Ser Pro Ser Leu Ile Ser Gln His Ile Leu Trp Lys Gln Glu Glu   1 5 10 15 Met Leu Ile Lys Arg Ile Arg Pro Ser Phe Pro              20 25       <210> 718 <211> 15 <212> PRT <213> Homo sapiens    <400> 718 Asn Gln Tyr Leu Ala Pro Tyr Ile Ser Leu Val Lys Leu Val Ile   1 5 10 15       <210> 719 <211> 16 <212> PRT <213> Homo sapiens    <400> 719 Ser Cys Gln Ile Arg His Ser Val Lys Gly Lys His Arg Asn Trp Leu   1 5 10 15       <210> 720 <211> 34 <212> PRT <213> Homo sapiens    <400> 720 Val Lys Pro Ser Ser Gln Gln Gln Gly Leu Glu Ile Thr Phe Glu Ala   1 5 10 15 Tyr Cys Thr Gly Leu His Gln Lys Met Ser Ala Leu Leu Ile Ala Lys              20 25 30 Asn Val       <210> 721 <211> 14 <212> PRT <213> Homo sapiens    <400> 721 His Arg Thr Ala Leu Gly Leu Ile Cys Leu Gln Glu Glu Ile   1 5 10       <210> 722 <211> 13 <212> PRT <213> Homo sapiens    <400> 722 Thr Leu Arg Leu Val Phe Thr Tyr Ser Ser Ser Ile Glu   1 5 10       <210> 723 <211> 5 <212> PRT <213> Homo sapiens    <400> 723 His Ala Ser Glu Phe   1 5       <210> 724 <211> 6 <212> PRT <213> Homo sapiens    <400> 724 Val Ala Lys Val Ser Glu   1 5       <210> 725 <211> 27 <212> PRT <213> Homo sapiens    <400> 725 Phe Phe Met Cys Ile Phe Cys Arg Met Phe Trp Phe Lys Lys Glu Cys   1 5 10 15 Leu Lys Leu Phe Lys Arg Leu Gln Phe Leu Met              20 25       <210> 726 <211> 65 <212> PRT <213> Homo sapiens    <400> 726 Leu Tyr Pro Ser Ala Trp Lys Ile Ile Thr Asn Met Ala Ala Val Asp   1 5 10 15 Phe Leu Val Val Ser Ser Ala Thr Cys Arg Gly Leu Leu Tyr His Ile              20 25 30 Val Leu Gly Cys Arg Thr Leu Val Phe Leu Gly Val Leu His Gly Leu          35 40 45 His Tyr Leu Gln His Cys Thr Ile Thr Thr Arg Lys Gly Ser Ile Leu      50 55 60 His  65       <210> 727 <211> 16 <212> PRT <213> Homo sapiens    <400> 727 Cys Leu Ser Gly Asn Asn His Phe Cys Val Ile Met Glu Gly Phe Leu   1 5 10 15       <210> 728 <211> 10 <212> PRT <213> Homo sapiens    <400> 728 Cys Met Lys Leu Val Phe Phe Ile Tyr Lys   1 5 10       <210> 729 <211> 8 <212> PRT <213> Homo sapiens    <400> 729 Cys Leu Phe Ser Ser Val Asn Ser   1 5       <210> 730 <211> 59 <212> PRT <213> Homo sapiens    <400> 730 Val Cys Thr Arg Gly Thr Thr Ser Asp Leu Leu Gln Cys Ser Val Leu   1 5 10 15 Val Phe Thr Phe Ile Leu Lys Ala Phe Ser Phe Ala Phe Asn Phe Met              20 25 30 Tyr Leu Ser Ser Glu Leu Asp Leu Gln Met Cys Thr Asp Ser Ser Tyr          35 40 45 Leu Cys Ile Ala His Asn His Ala Ile Gln His      50 55       <210> 731 <211> 7 <212> PRT <213> Homo sapiens    <400> 731 Cys Tyr Ile Val Leu Cys Lys   1 5       <210> 732 <211> 6 <212> PRT <213> Homo sapiens    <400> 732 Lys Pro Cys Thr Glu Gly   1 5       <210> 733 <211> 5 <212> PRT <213> Homo sapiens    <400> 733 Ile Phe Leu Gln Asn   1 5       <210> 734 <211> 22 <212> PRT <213> Homo sapiens    <400> 734 Tyr Gly Asp Trp Gln Glu Phe Leu Arg Phe Glu Ser Ser Ser Asp Val   1 5 10 15 Lys Met Glu Asp Ser Val              20       <210> 735 <211> 25 <212> PRT <213> Homo sapiens    <400> 735 Ser Leu Tyr Phe Gln Gly Ile Leu Ile Asn Ile Phe Ile Arg His Leu   1 5 10 15 Pro Val Ser Leu Lys Tyr Phe Leu Phe              20 25       <210> 736 <211> 6 <212> PRT <213> Homo sapiens    <400> 736 Leu Lys Asn Val Ser Gln   1 5       <210> 737 <211> 102 <212> PRT <213> Homo sapiens    <400> 737 Met Leu Asp Lys Phe Val Phe Leu Ser Phe Ser Val Val Thr Gln Pro   1 5 10 15 Ser Pro Ser Val Ser Gln Pro Ser Thr Ser Gln Ser Glu Glu Lys Ala              20 25 30 Pro Glu Leu Pro Lys Pro Lys Lys Asn Arg Cys Phe Met Cys Arg Lys          35 40 45 Lys Val Gly Leu Thr Gly Phe Asp Cys Arg Cys Gly Asn Leu Phe Cys      50 55 60 Gly Leu His Arg Tyr Ser Asp Lys His Asn Cys Pro Tyr Asp Tyr Lys  65 70 75 80 Ala Glu Ala Ala Ala Lys Ile Arg Lys Glu Asn Pro Val Val Val Ala                  85 90 95 Glu Lys Ile Gln Arg Ile             100       <210> 738 <211> 13 <212> PRT <213> Homo sapiens    <400> 738 Ile Thr Ser Cys Glu Glu Thr Glu Thr Leu Phe Leu Phe   1 5 10       <210> 739 <211> 6 <212> PRT <213> Homo sapiens    <400> 739 Tyr Ile Val Gly Lys His   1 5       <210> 740 <211> 22 <212> PRT <213> Homo sapiens    <400> 740 Arg Ala Asp Ala Trp Pro Phe Phe Phe Asp Val Leu Gln Ser Phe Thr   1 5 10 15 Leu His Leu Ser Val Leu              20          <210> 741 <211> 11 <212> PRT <213> Homo sapiens    <400> 741 Asp Val Trp Val Phe Val Thr Gly Arg Ile Gly   1 5 10       <210> 742 <211> 15 <212> PRT <213> Homo sapiens    <400> 742 Ile Gln Pro Tyr Lys Cys Ile Cys Pro Pro Leu Lys Lys Ile Gly   1 5 10 15       <210> 743 <211> 10 <212> PRT <213> Homo sapiens    <400> 743 Lys Ser Ala Gln Gln Ser Glu Thr His Arg   1 5 10       <210> 744 <211> 11 <212> PRT <213> Homo sapiens    <400> 744 Glu Gln Asn Val Val Pro Met Cys Gln Thr Lys   1 5 10       <210> 745 <211> 22 <212> PRT <213> Homo sapiens    <400> 745 Met Lys Ser Leu His Val Cys Ser Ile Ser Ala Phe Trp Glu Cys Asn   1 5 10 15 Gln Gly Ile Ile Phe Gly              20       <210> 746 <211> 7 <212> PRT <213> Homo sapiens    <400> 746 Cys Tyr Val Pro Val Phe Phe   1 5       <210> 747 <211> 20 <212> PRT <213> Homo sapiens    <400> 747 Asn Gly Thr Pro Glu Lys Asp Trp Gln Ser Thr Ser Thr Ile Val Lys   1 5 10 15 Leu His Pro Leu              20       <210> 748 <211> 13 <212> PRT <213> Homo sapiens    <400> 748 Phe His Asn Ile Phe Phe Gly Ser Arg Lys Lys Cys Ser   1 5 10       <210> 749 <211> 16 <212> PRT <213> Homo sapiens    <400> 749 Arg Gly Ser Asp Leu Leu Ser Arg Glu Thr Ser Ile Trp Arg His Ile   1 5 10 15       <210> 750 <211> 11 <212> PRT <213> Homo sapiens    <400> 750 Ala Trp Leu Asn Trp Ser Ser Lys Ala Val Lys   1 5 10       <210> 751 <211> 9 <212> PRT <213> Homo sapiens    <400> 751 Lys Val Asn Ile Glu Thr Gly Tyr Lys   1 5       <210> 752 <211> 10 <212> PRT <213> Homo sapiens    <400> 752 Asn His Gln Ala Asn Asn Arg Val Leu Arg   1 5 10       <210> 753 <211> 27 <212> PRT <213> Homo sapiens    <400> 753 Pro Leu Lys Leu Ile Val Leu Ala Cys Thr Arg Arg Cys Leu His Tyr   1 5 10 15 Ser Leu Leu Lys Met Cys Ser Thr Glu Leu His              20 25          <210> 754 <211> 51 <212> PRT <213> Homo sapiens    <400> 754 Phe Val Tyr Lys Lys Lys Phe Lys Leu Tyr Val Trp Phe Ser His Thr   1 5 10 15 Ala Ala Leu Leu Asn Asn Met His Leu Asn Phe Lys Leu Gln Arg Tyr              20 25 30 Leu Asn Asn Phe Ser Cys Ala Ser Phe Val Glu Cys Phe Gly Ser Arg          35 40 45 Lys Asn Val      50       <210> 755 <211> 8 <212> PRT <213> Homo sapiens    <400> 755 Ser Phe Leu Lys Asp Phe Ser Ser   1 5       <210> 756 <211> 10 <212> PRT <213> Homo sapiens    <400> 756 Cys Asn Cys Thr Leu Leu His Gly Lys Ser   1 5 10       <210> 757 <211> 5 <212> PRT <213> Homo sapiens    <400> 757 Pro Thr Trp Leu Gln   1 5       <210> 758 <211> 20 <212> PRT <213> Homo sapiens    <400> 758 Trp Tyr Pro Ala Pro Leu Ala Glu Gly Cys Phe Ile Ile Leu Tyr Leu   1 5 10 15 Gly Val Gly Leu              20       <210> 759 <211> 16 <212> PRT <213> Homo sapiens    <400> 759 Cys Ser Trp Val Tyr Cys Met Gly Cys Ile Ile Tyr Ser Ile Val Gln   1 5 10 15       <210> 760 <211> 20 <212> PRT <213> Homo sapiens    <400> 760 Gln Leu Glu Lys Ala Val Tyr Phe Thr Asp Ala Cys Leu Val Ile Ile   1 5 10 15 Thr Ser Val Leu              20       <210> 761 <211> 7 <212> PRT <213> Homo sapiens    <400> 761 Trp Lys Val Phe Cys Asp Val   1 5       <210> 762 <211> 11 <212> PRT <213> Homo sapiens    <400> 762 Asn Leu Cys Phe Leu Tyr Ile Asn Glu Tyr Ser   1 5 10       <210> 763 <211> 9 <212> PRT <213> Homo sapiens    <400> 763 Cys Cys Gly Asn Ala Cys Phe His Leu   1 5       <210> 764 <211> 18 <212> PRT <213> Homo sapiens    <400> 764 Ile Val Lys Tyr Val His Glu Ala Leu Leu Leu Ile Tyr Cys Asn Val   1 5 10 15 Gln Ser       <210> 765 <211> 21 <212> PRT <213> Homo sapiens    <400> 765 Phe Leu Leu Leu Phe Leu Lys His Ser Val Leu Leu Ser Ile Leu Cys   1 5 10 15 Thr Leu Val Leu Ser              20       <210> 766 <211> 37 <212> PRT <213> Homo sapiens    <400> 766 Thr Cys Arg Cys Val Gln Ile Val His Ile Tyr Val Leu His Ile Ile   1 5 10 15 Met Leu Phe Ser Ile Asp Ala Ile Leu Tyr Tyr Val Asn Asn Lys Ser              20 25 30 His Val Gln Arg Glu          35       <210> 767 <211> 4948 <212> DNA <213> Homo sapiens    <400> 767 gtccgaccgc gctcgccttc cttgcagccg cgccccggcc ccatggacgc cctgtgcggt 60 tccggggagc tcggctccaa gttctgggac tccaacctgt ctgtgcacac agaaaacccg 120 gacctcactc cctgcttcca gaactccctg ctggcctggg tgccccgcat ctacctgtgg 180 gtcgccctgc cctgctactt gctctacctg cggcaccatt gtcgtggcta catcatcctc 240 tcccacctgt ccaagctcaa gatggtcctg ggtgtcctgc tgtggtgcgt ctcctgggcg 300 gacctttttt actccttcca tggcctggtc catggccggg cccctgcccc tgttttcttt 360 gtcaccccct tggtggtggg ggtcaccatg ctgctggcca ccctgctgat acagtatgag 420 cggctgcagg gcgtacagtc ttcgggggtc ctcattatct tctggttcct gtgtgtggtc 480 tgcgccatcg tcccattccg ctccaagatc cttttagcca aggcagaggg tgagatctca 540 gaccccttcc gcttcaccac cttctacatc cactttgccc tggtactctc tgccctcatc 600 ttggcctgct tcagggagaa acctccattt ttctccgcaa agaatgtcga ccctaacccc 660 taccctgaga ccagcgctgg ctttctctcc cgcctgtttt tctggtggtt cacaaagatg 720 gccatctatg gctaccggca tcccctggag gagaaggacc tctggtccct aaaggaagag 780 gacagatccc agatggtggt gcagcagctg ctggaggcat ggaggaagca ggaaaagcag 840 acggcacgac acaaggcttc agcagcacct gggaaaaatg cctccggcga ggacgaggtg 900 ctgctgggtg cccggcccag gccccggaag ccctccttcc tgaaggccct gctggccacc 960 ttcggctcca gcttcctcat cagtgcctgc ttcaagctta tccaggacct gctctccttc 1020 atcaatccac agctgctcag catcctgatc aggtttatct ccaaccccat ggccccctcc 1080 tggtggggct tcctggtggc tgggctgatg ttcctgtgct ccatgatgca gtcgctgatc 1140 ttacaacact attaccacta catctttgt actgggtga agtttcgtac tgggatcatg 1200 ggtgtcatct acaggaaggc tctggttatc accaactcag tcaaacgtgc gtccactgtg 1260 ggggaaattg tcaacctcat gtcagtggat gcccagcgct tcatggacct tgcccccttc 1320 ctcaatctgc tgtggtcagc acccctgcag atcatcctgg cgatctactt cctctggcag 1380 aacctaggtc cctctgtcct ggctggagtc gctttcatgg tcttgctgat tccactcaac 1440 ggagctgtgg ccgtgaagat gcgcgccttc caggtaaagc aaatgaaatt gaaggactcg 1500 cgcatcaagc tgatgagtga gatcctgaac ggcatcaagg tgctgaagct gtacgcctgg 1560 gagcccagct tcctgaagca ggtggagggc atcaggcagg gtgagctcca gctgctgcgc 1620 acggcggcct acctccacac cacaaccacc ttcacctgga tgtgcagccc cttcctggtg 1680 accctgatca ccctctgggt gtacgtgtac gtggacccaa acaatgtgct ggacgccgag 1740 aaggcctttg tgtctgtgtc cttgtttaat atcttaagac ttcccctcaa catgctgccc 1800 cagttaatca gcaacctgac tcaggccagt gtgtctctga aacggatcca gcaattcctg 1860 agccaagagg aacttgaccc ccagagtgtg gaaagaaaga ccatctcccc aggctatgcc 1920 atcaccatac acagtggcac cttcacctgg gcccaggacc tgccccccac tctgcacagc 1980 ctagacatcc aggtcccgaa aggggcactg gtggccgtgg tggggcctgt gggctgtggg 2040 aagtcctccc tggtgtctgc cctgctggga gagatggaga agctagaagg caaagtgcac 2100 atgaagggct ccgtggccta tgtgccccag caggcatgga tccagaactg cactcttcag 2160 gaaaacgtgc ttttcggcaa agccctgaac cccaagcgct accagcagac tctggaggcc 2220 tgtgccttgc tagctgacct ggagatgctg cctggtgggg atcagacaga gattggagag 2280 aagggcatta acctgtctgg gggccagcgg cagcgggtca gtctggctcg agctgtttac 2340 agtgatgccg atattttctt gctggatgac ccactgtccg cggtggactc tcatgtggcc 2400 aagcacatct ttgaccacgt catcgggcca gaaggcgtgc tggcaggcaa gacgcgagtg 2460 ctggtgacgc acggcattag cttcctgccc cagacagact tcatcattgt gctagctgat 2520 ggacaggtgt ctgagatggg cccgtaccca gccctgctgc agcgcaacgg ctcctttgcc 2580 aactttctct gcaactatgc ccccgatgag gaccaagggc acctggagga cagctggacc 2640 gcgttggaag gtgcagagga taaggaggca ctgctgattg aagacacact cagcaaccac 2700 acggatctga cagacaatga tccagtcacc tatgtggtcc agaagcagtt tatgagacag 2760 ctgagtgccc tgtcctcaga tggggaggga cagggtcggc ctgtaccccg gaggcacctg 2820 ggtccatcag agaaggtgca ggtgacagag gcgaaggcag atggggcact gacccaggag 2880 gagaaagcag ccattggcac tgtggagctc agtgtgttct gggattatgc caaggccgtg 2940 gggctctgta ccacgctggc catctgtctc ctgtatgtgg gtcaaagtgc ggctgccatt 3000 ggagccaatg tgtggctcag tgcctggaca aatgatgcca tggcagacag tagacagaac 3060 aacacttccc tgaggctggg cgtctatgct gctttaggaa ttctgcaagg gttcttggtg 3120 atgctggcag ccatggccat ggcagcgggt ggcatccagg ctgcccgtgt gttgcaccag 3180 gcactgctgc acaacaagat acgctcgcca cagtccttct ttgacaccac accatcaggc 3240 cgcatcctga actgcttctc caaggacatc tatgtcgttg atgaggttct ggcccctgtc 3300 atcctcatgc tgctcaattc cttcttcaac gccatctcca ctcttgtggt catcatggcc 3360 agcacgccgc tcttcactgt ggtcatcctg cccctggctg tgctctacac cttagtgcag 3420 cgcttctatg cagccacatc acggcaactg aagcggctgg aatcagtcag ccgctcacct 3480 atctactccc acttttcgga gacagtgact ggtgccagtg tcatccgggc ctacaaccgc 3540 agccgggatt ttgagatcat cagtgatact aaggtggatg ccaaccagag aagctgctac 3600 ccctacatca tctccaaccg gtggctgagc atcggagtgg agttcgtggg gaactgcgtg 3660 gtgctctttg ctgcactatt tgccgtcatc gggaggagca gcctgaaccc ggggctggtg 3720 ggcctttctg tgtcctactc cttgcaggtg acatttgctc tgaactggat gatacgaatg 3780 atgtcagatt tggaatctaa catcgtggct gtggagaggg tcaaggagta ctccaagaca 3840 gagacagagg cgccctgggt ggtggaaggc agccgccctc ccgaaggttg gcccccacgt 3900 ggggaggtgg agttccggaa ttattctgtg cgctaccggc cgggcctaga cctggtgctg 3960 agagacctga gtctgcatgt gcacggtggc gagaaggtgg ggatcgtggg ccgcactggg 4020 gctggcaagt cttccatgac cctttgcctg ttccgcatcc tggaggcggc aaagggtgaa 4080 atccgcattg atggcctcaa tgtggcagac atcggcctcc atgacctgcg ctctcagctg 4140 accatcatcc cgcaggaccc catcctgttc tcggggaccc tgcgcatgaa cctggacccc 4200 ttcggcagct actcagagga ggacatttgg tgggctttgg agctgtccca cctgcacacg 4260 tttgtgagct cccagccggc aggcctggac ttccagtgct cagagggcgg ggagaatctc 4320 agcgtgggcc agaggcagct cgtgtgcctg gcccgagccc tgctccgcaa gagccgcatc 4380 ctggttttag acgaggccac agctgccatc gacctggaga ctgacaacct catccaggct 4440 accatccgca cccagtttga tacctgcact gtcctgacca tcgcacaccg gcttaacact 4500 atcatggact acaccagggt cctggtcctg gacaaaggag tagtagctga atttgattct 4560 ccagccaacc tcattgcagc tagaggcatc ttctacggga tggccagaga tgctggactt 4620 gcctaaaata tattcctgag atttcctcct ggcctttcct ggttttcatc aggaaggaaa 4680 tgacaccaaa tatgtccgca gaatggactt gatagcaaac actgggggca ccttaagatt 4740 ttgcacctgt aaagtgcctt acagggtaac tgtgctgaat gctttagatg aggaaatgat 4800 ccccaagtgg tgaatgacac gcctaaggtc acagctagtt tgagccagtt agactagtcc 4860 ccggtctccc gattcccaac tgagtgttat ttgcacactg cactgttttc aaataacgat 4920 tttatgaaat gaaaaaaaaa aaaaaaaa 4948       <210> 768 <211> 3648 <212> DNA <213> Homo sapiens    <400> 768 aaaagagaca ttgtaatgag gcacaccact aaagtgagca tgcccaatta aaaccagtgt 60 aatataggat aagaaaatct gatttttcaa aaaagatact ctacataaag aatccttcat 120 ataaaaagtt ctttcttgta gtacatttaa agttttaatt cactcatgta taactgagag 180 ttcctttgag ccctttttag gcagggaggc atgtctgtca tctagcgtgt ggcccagtaa 240 gtgattatta cattggaatc agtttttcag tcttttaaaa taaattctat gccataagaa 300 taaaagataa agagcaaaat taatgttaac tatttttagc ttattataac tatgtcaaca 360 agtgtttatt aatacctatt atgggaaagt cactgtggtt ggcattgaaa attacatcat 420 ctttaaagca gtatttgtcc ccagatggac tcatcactag caaagactag gttcattgga 480 aggcataggg tgagagaatg ggaagatgga gtggaggcgg gttgttaaag tgctgtcagt 540 gagtgatttt gtctacttga ataatggtcc atgtttgggg gcatattgtg tttcataaga 600 agtgaaaggt atttgcaaag taagctacaa atgacccata aatctgttaa caacagtcct 660 taatatgcaa agatgaaaac caagcattac tgctacccaa agggaactgg tgcttggtga 720 tgtgcagatg gggctgttgg ttaagagagc tattacaggt tttctctctt aggtttcata 780 ggaggtagtt actgagatga gattgtttta tctttttgaa tacagatctc ttgtcttgag 840 ttagttctga ggatgggagt aataaaggag ttttttgttt ttttgtttgt ttgtttgttt 900 tggctcctta gtaatactcc tctgacattt atttctatta ttcttcaaag aaaggaaacc 960 aactgaaatg tttgctttaa caaacatttt aataagttct ctgggttttt ttttcccctt 1020 ttaaaaaaat tagcatatac catagcaata aaagaactaa tgttaactat tgtatgctac 1080 aacttaagtg atttttctaa agaagcacaa tgtcattgaa agtattattg aaaaggatca 1140 tagtcacatt gaatttgtga aggccaaaga aattgaaggg agtgatattt tcattttatg 1200 atattcacat tagtaaattt tgtgtacaag aataccaggc agagtgtttt acccatggaa 1260 acaggtttca gattactttg tttttactgt tagagtctca agtttagaaa tgctaacact 1320 taaatcagtt tttttctcac tatacttgaa gattgttaat attttgatat cttcctagct 1380 tgatgaattt aaacatatct tcagatctgt gacagtgaca gccaatagga ctgataatat 1440 tagcttcaaa ccaataatat ccagggttaa aataaaaatc atagtgaaag tacgattgta 1500 aaattatgct atattaactt ttaagtctgt aataacttga catcaaaatg ttatgtaatt 1560 accataaata atggctagcg agaacatctt tggaaattct caaattacct ttcttactac 1620 actgtttgca gaatgaatgt agaaatgatc ctgttagctt tctgaatgtt ctgtgggttg 1680 aatgtgtttt tgcttaaata aagcttttgg tatttgttta aattacactt cttgagaagt 1740 ggaaatttta ggatcatctt tgctttgttt cagttttgtg atttttgaaa tgaatgttta 1800 gtttactgag ccagttggtc atttcttcct catgtcgtta agtccagtga gtaagcctga 1860 actgtgaata aattaccaaa aacttgctta gaatttcatt ttgaagcaat ttgctaatat 1920 ttgaagtgta tacacatttg tagttatgtt aaaaattgta ttgtactaag aatgtaatca 1980 atgtctactt tagttgtaaa catttctgat gtcaaaactt tattcattac tgttgatttt 2040 aagaataaga aatcactgcc taaatattac caaaagccac tgtctctacc cgaacttccc 2100 agtttgggaa agaatcgtta gataaaacaa aggctctgcc ctttctgata ccaaactcca 2160 cagatacttt ctcacatctt ttaaaacatt ttgcaataac atattgttta taggaagttt 2220 acagggtatg caatgattaa aacttttaag tgaattgata gttgcaaaag aaaggataat 2280 atttaaggtc agtgagtagc aagacaatct aaagtttctg taatatctgg ctctctgtta 2340 attatagagc aaagtttccc ttacagaatc cttttatgaa cagcaagcta gagtctatcc 2400 ctagtggtta tagcacctgc tgcgtttttc aggagacagt taggccaggg tgatttgaat 2460 ggatagatgt gctgttttgc ctgcttgtag aattcagccc agtctttggt ctctctctct 2520 ctctccctcc tccacctctc cctctctctt cttctgcacc agagcctaag gctgcgccac 2580 caagatgcgt cattttttcc agaggcttct tttttttttt ttttgagatg gagttttgct 2640 ctgttgccca ggctggcatg cagtgctgca atcttggctg actgcaactt ccacctcccg 2700 tgttcacacg agtcttttgc ctcagcctct ggattagctg ggattacagg cacgtgccac 2760 catgcctagc taatttttgt gtttttagta gagacggggt ttcaccatgt tggccaggct 2820 agtctcaaac tcctgacctt aagtgatctg cccgccttgg cctcccaaag tgctgggatt 2880 acaggcatga gtcaccgtgt cctgcccaga catatcaaat ttgacaggta ttgtataccc 2940 tttggatctt taggaattaa tttttgcctc tgtcactcag ctttgtatat tttgaaatgg 3000 agataagtat agggaggtct tggaaggaaa attgccagaa ttcccaaacc atgtaacact 3060 cattgagaat tccagatcca ttatatctaa agggcaagtg aaggaaacag tattgtgaac 3120 tgggtataac tccttggttc ttaactagta cattcttaat ctgtgagacc caaaggttga 3180 taaacaataa tttaagattg tacagtactc taaacgtctg caaaggtcta gatgttatca 3240 gtatcactag tttttatttc tgccagtagc tcccttttag gttacattgt tgtcctcttt 3300 ccagtgtggc atctgtcatt ggtttttcac tatggcaagt tcattaaaaa gcttgctcca 3360 ttgttatctt caagtaatgc ccataaggag atggaagata tctgagacaa ttaaggcttt 3420 agcttctagg caagagaaat aacgttgcat taaatttcaa gtttctttct gctagacttg 3480 aatgtgtcta gccactctaa tttatggggg cttttggttt tttcctattg tactttgtat 3540 gtagaattgt tttgaaatat caagcatatt tactttgaat ttgaactctt tcttaatttt 3600 gtatttatcc tttgaataaa atgtaaatcc aaaaaaaaaa aaaaaaaa 3648       <210> 769 <211> 978 <212> DNA <213> Homo sapiens    <400> 769 ctaatatgtg aagtcagtca ttagtctgca taatctctgt ctccctctgt gtgtgtcttt 60 ctataaagca catgtgtaca cacacacaca caaatatact gaaagctagg gtaagttcta 120 aactgaatat caaaaaccaa aatcaagaac aaagaagtga tattttccaa acaaacatgg 180 attccctccc aaagtgctgg gattacaggc atgagtcacc gtgtcctgcc cagacatatc 240 aaatttgaca ggtattgtat accctttgga tctttaggaa ttaatttttg cctctgtcac 300 tcagctttgt atattttgaa atggagataa gtatagggag gtcttggaag gaaaattgcc 360 agaattccca aaccatgtaa cactcattga gaattccaga tccattatat ctaaagggca 420 agtgaaggaa acagtattgt gaactgggta taactccttg gttcttaact agtacattct 480 taatctgtga gacccaaagg ttgataaaca ataatttaag attgtcagta ctctaaacgt 540 ctgcaaaggt ctagatgtta tcagtatcac tagtttttat ttctgccagt agctcccttt 600 taggttacat tgttgtcctc tttccagtgt ggcatctgtc attggttttt cactatggca 660 agttcattaa aaagcttgct ccattgttat cttcaagtaa tgcccataag gagatggaag 720 atatctgaga caattaaggc tttagcttct aggcaagaga aataacgttg cattaaattt 780 caagtttctt tctgctagac ttgaatgtgt ctagccactc taatttatgg gggcttttgg 840 ttttttccta ttgtactttg tatgtagaat tgttttgaaa tatcaagcat atttactttg 900 aatttgaact ctttcttaat tttgtattta tcctttgaat aaaatgtaaa tccaaaaaaa 960 aaaaaaaaaa aaaaaaaa 978          <210> 770 <211> 2431 <212> DNA <213> Homo sapiens    <400> 770 aagaagtcat gtctgctgtt tgtcttggga tggagctgcc ggggacacgg cccctcccac 60 cacaagtggc caagggcatg ttgtggtcgg gaagcttcac cggtcggccc cggccacctc 120 acctctgcct gccactcggg gtcctgggcc ctgctgcccc ccgagtgcag ctgcaacgcc 180 ccttttgcct aaagcagcag gccctgccga cagggacctg agcatctttt tcttccttcc 240 ttggcctctg aggtcctgag agggaactcc ccaactctcc cgccccagtc agcggtcaca 300 ggggagtctc tgggcccaca acagggccgg cctggtggct gagaccttgg tggctcctgg 360 ccacgctcag gaaggcccgt gtggtcaggg ctgcatttga accggccccg cactggggat 420 ctgccgaggg ctgggtgctg atgtccccac cgcgcccccc gtcgatgtct cttgccaggc 480 gcgactcttc gatgaaccgc agctggccag cctgtgcctg gagaacatcg acaaaaacac 540 tgcagacgcc atcaccgcgg agggcttcac cgacattgac ctggacacgc tggtggctgt 600 cctggagcgc gacacactgg gcatccgtga ggtgcggctg ttcaatgccg ttgtccgctg 660 gtccgaggcc gagtgtcagc ggcagcagct gcaggtgacg ccagagaaca ggcggaaggt 720 tctgggcaag gccctgggcc tcattcgctt cccgctcatg accatcgagg agttcgctgc 780 aggtcccgca cagtcgggca tcctggtgga ccgcgaggtg gtcagcctct tcctgcactt 840 caccgtcaac cccaagccac gagtggagtt cattgaccgg ccccgctgct gcctgcgtgg 900 gaaggagtgc agcatcaacc gcttccagca ggtggagagt cgctggggct acagcgggac 960 cagtgaccgc atcaggttct cagtcaacaa gcgcatcttc gtggtgggat ttgggctgta 1020 tggatccatc cacgggccca ccgactacca agtgaacatc cagattattc acaccgatag 1080 caacaccgtc ttgggccaga acgacacggg cttcagctgc gacggctcag ccagcacctt 1140 ccgcgtcatg ttcaaggagc cggtggaggt gctgcccaac gtcaactaca cggcctgtgc 1200 cacgctcaag ggcccagact cccactacgg caccaaaggc ctgcgcaagg tgacacacga 1260 gtcgcccacc acgggcgcca agacctgctt caccttttgc tacgcggccg ggaacaacaa 1320 tggcacatcc gtggaggacg gccagatccc cgaggtcatc ttctacacct aggctgcccg 1380 acaccgacac cgccctccct ccgtggggat agccgagccc caggccatca tctgctgctg 1440 gggccccccc accacgcggt gccaggccca gtgtccccca ggccgtctgt ccactccatg 1500 ccacctttct cagcatcagg acggggttgc cctgtgttca ccacgagtgt ggctgctgga 1560 tcagggcagc cggggaggtg gccaggccag tggccaggcc ctgtggagac aatccctcag 1620 gactagggac agggctgtgc cggcctgggc cagggcccac ggacccgcag ctcagggcgc 1680 ctgcccacgt cgtctgccgg cggtgcgccg cgggcgtccc tcgcgtctct tcactgcaca 1740 ttgcaatgca tttgcgattc ccatttctct gctaggagcc agcctgggtg gcgctgctcc 1800 cagagccgtg ggtcccagac cttgcgttcc ttttgttcct gtccgtttat caggacacgg 1860 gccccacctg tcacgtgccc gaggccaccc aagcccagcc tgcggggcgt tcccactgcc 1920 tggatgccgg cttgagttct gcgcacgcag gattcagtgt ggggacggcc cctgccggat 1980 aggcctagcc ctggcccagg tggtgagcgg tttgcagtgt ccgttctcat ccacctgatg 2040 ggcccagata aaggcccccg ctgtccagcc tccctggacg gccctcgcgg tccctgcagc 2100 ccaagatggg actcagaccc tgtgccccag agctcccctg ccgcagaatg gggccccagc 2160 cggccccgac cgggtccagg agcactgctc gcctgtacat actgttgccc tagcccacct 2220 ggtgccgtgg gagccacccc caggtgctgg gggcacaagc ccctccccac tccgggccac 2280 ggcccccacc caccccgcgt gtttctgccc tgtgactcct ggaacctgcg tcctccccaa 2340 agccatggga ggggtgtcct cctcagacca tgcccccaga tgattttttt aaataaagaa 2400 acaaatgcac ctgcaaaaaa aaaaaaaaaa a 2431       <210> 771 <211> 4200 <212> DNA <213> Homo sapiens    <400> 771 attttattca acacatcatt ctgaaagaac gtgtggaaaa ctaatgactg agcttctaga 60 ccaatggtga gtaatggacc gaggcagttt cctggacaat tttattgtct tggttcctgg 120 atgggcttta cctctttctt cccaaggaca tcccaaactg aatgtgagtg actggatgtg 180 actgagaatg acaaaaaaga ctgtcggcaa gtgtgtaagt aaatggactg agtgattttg 240 atcgcatata agtatgaaat tcagagtgta tgcaaaggag tgtttgaatg agggtggtgt 300 gagtgtccgt gtgattggaa acatcgtgtc actgggaaga aaatttcggg agctagggaa 360 tggggtaaag tgaggagtgt ttaagggtga atgtttttga gtctgtgcta gtaacgggtt 420 cgtgatggtt cccaggaggg gacatctggg ggatccacgg ctcctcccgc ctcgccgaat 480 gctctcccca caccactcca cactgttgag gcagttgaca ggagccgcag aagaaacaag 540 ggacatcctc actcctgagc cgctccgtgg tcttcactct ccttgacctt tttagttccg 600 gggagaagcg actctggagc ggctcaggag tgaggatgtc ccttgtttct tctgcggctc 660 ctgtcaactg cctcaacagt gtggagtggt gtggggagag cattcggcga ggcgggagga 720 gccgtggatc ccccagatgt cccctcctgg gaaccatcac gaacccgtta ctagcacaga 780 ctcaaaaaca ttcaccctta aacactcctc actttacccc attccctagc tcccgaaatt 840 ttcttcccag tgacacgatg tttccaatca cacggacact cacaccaccc tcattcaaac 900 actcctttgc atacactctg aatttcatac ttatatgcga tcaaaatcac tcagtccatt 960 tacttacaca cttgccgaca gtcttttttg tcattctcag tcacatccag tcactcacat 1020 tcagtttggg atgtccttgg gaagaaagag gtaaagccca tccaggaacc aagacaataa 1080 aattgtccag gaaactgcct cggtccatta ctcaccattg gtctagaagc tcagcattac 1140 ccacacattt actaaatgtc aggcactaga acatagtagc caagacagac tggtcacgac 1200 tttcaaggag ctcataatgg agtcagtagt ggtttcctga tggacctaat taaaggtccc 1260 tagctgtccc tcctgccttt cctacatact gcttgctata taaaattctt gtcaaggttg 1320 atgtaagtta ctggttcaga tcccatctgt cagtcccttc ctggccctca tttgaattct 1380 gtgcttttca atgcttttct ttctttgcca ctgccatctc aggaagcttt tataggaaaa 1440 ggtctttctg gctcacccca tcccctccca attcccagct tctgatggaa ttgagcaagg 1500 ggtggggctt agtcagactg ctggagccag cctctcgctt gtcctaggat tctctgccta 1560 agcttaagga cctggcattt ctcaagaacc agctggaaag cctgcagcgg cgtgtagaag 1620 acgaagtcaa cagtggagtg ggccaggatg gctcgctgtt gtcctccccg ttcctcaagg 1680 gattcctggc tggctatgtg gtggccaaac tgagggcatc agcagtattg ggctttgctg 1740 tgggcacctg cactggcatc tatgcggctc aggcatatgc tgtgcccaac gtggagaaga 1800 cattaaggga ctatttgcag ttgctacgca aggggcccga ctagctctag gtgccatgga 1860 agaggcagga tgagcagctc agccttcagg tggagacact ttatctggat tccccagctg 1920 tcatccattt gctatctcca actttcctgc caccttcatc cttgcctccc ttcctgcaga 1980 ttgtggacag tagttcctca gcctgcaccc tggattcctt cttccccttc ctagctccat 2040 gggactcgcc ccaagactgt ggcttcaagg accaccagcc ccttactctt caagccctga 2100 ctgtggagtt ggtagatgcc tctgatcctc agtattctct ctggcaatgt tccacggctt 2160 ctccttcctg ggagctggct ccataacttg attttcccca aacgtgttgc aatccctgct 2220 gccccttagc cacccagggt cttgtgtggg tatgagtgta gaggatgggg gtatgccagg 2280 cctgggccgt cccaggcagg cccgctggac cctgatgcta ctcctatcca ctgccatgta 2340 cggtgcccat gccccattgc tggcactgtg ccatgtggac ggccgagtgc ccttccggcc 2400 ctcctcagcc gtgctgctga ctgagctgac caagctactg ttatgcgcct tctcccttct 2460 ggtaggctgg caagcatggc cccaggggcc cccaccctgg cgccaggctg ctcccttcgc 2520 actatcagcc ctgctctatg gcgctaacaa caacctggtg atctatcttc agcgttacat 2580 ggaccccagc acctaccagg tgctgagtaa tctcaagatt ggaagcacag ctgtgctcta 2640 ctgcctctgc ctccggcacc gcctctctgt gcgtcagggg ttagcgctgc tgctgctgat 2700 ggctgcggga gcctgctatg cagcaggggg ccttcaagtt cccgggaaca cccttcccag 2760 tccccctcca gcagctgctg ccagccccat gcccctgcat atcactccgc taggcctgct 2820 gctcctcatt ctgtactgcc tcatctcagg cttgtcgtca gtgtacacag agctgctcat 2880 gaagcgacag cggctgcccc tggcacttca gaacctcttc ctctacactt ttggtgtgct 2940 tctgaatcta ggtctgcatg ctggcggcgg ctctggccca ggcctcctgg aaggtttctc 3000 aggatgggca gcactcgtgg tgctgagcca ggcactaaat ggactgctca tgtctgctgt 3060 catgaagcat ggcagcagca tcacacgcct ctttgtggtg tcctgctcgc tggtggtcaa 3120 cgccgtgctc tcagcagtcc tgctacggct gcagctcaca gccgccttct tcctggccac 3180 attgctcatt ggcctggcca tgcgcctgta ctatggcagc cgctagtccc tgacaacttc 3240 caccctgatt ccggaccctg tagattgggc gccaccacca gatccccctc ccaggccttc 3300 ctccctctcc catcagcagc cctgtaacaa gtgccttgtg agaaaagctg gagaagtgag 3360 ggcagccagg ttattctctg gaggttggtg gatgaagggg tacccctagg agatgtgaag 3420 tgtgggtttg gttaaggaaa tgcttaccat cccccacccc caaccaagtt cttccagact 3480 aaagaattaa ggtaacatca atacctaggc ctgagaaata accccatcct tgttgggcag 3540 ctccctgctt tgtcctgcat gaacagagtt gatgaaagtg gggtgtgggc aacaagtggc 3600 tttccttgcc tactttagtc acccagcaga gccactggag ctggctagtc cagcccagcc 3660 atggtgcatg actcttccat aagggatcct cacccttcca ctttcatgca agaaggccca 3720 gttgccacag attatacaac cattacccaa accactctga cagtctcctc cagttccagc 3780 aatgcctaga gacatgctcc ctgccctctc cacagtgctg ctccccacac ctagcctttg 3840 ttctggaaac cccagagagg gctgggcttg actcatctca gggaatgtag cccctgggcc 3900 ctggcttaag ccgacactcc tgacctctct gttcaccctg agggctgtct tgaagcccgc 3960 tacccactct gaggctccta ggaggtacca tgcttcccac tctggggcct gcccctgcct 4020 agcagtctcc cagctcccaa cagcctgggg aagctctgca cagagtgacc tgagaccagg 4080 tacaggaaac ctgtagctca atcagtgtct ctttaactgc ataagcaata agatcttaat 4140 aaagtcttct aggctgtagg gtggttccta caaccacagc caaaaaaaaa aaaaaaaaaa 4200       <210> 772 <211> 2952 <212> DNA <213> Homo sapiens    <400> 772 gagccttcga cggggcgggt gggctttgct gccgagcagg cggcgccgtc ttggggccta 60 gcggcgaggc gacccgcaca gtactgtaag attgatgtta aaggcatggt gttcacccca 120 cttcatcagc gtacataagt tatctcttct tttggaccct tattttatgc cataatgtat 180 gtcattgaaa gtgcccgaca gagacctcct aaaaggaaat acctatcaag tggaagaaaa 240 tctgtatttc aaaaacttta tgacttgtat attgaagaat gtgaaaaaga acctgaagtt 300 aagattccga gaccattcga ctgccctatg aagaaggaga gttgcttgaa tatttggatg 360 cagaagaatt acctcctatt ttggttgatc tcctagaaaa atctcaggtt aatatttttc 420 attgcggatg tgtcatagca gaaatacgtg actacaggca gtccagtaac atgaaatctc 480 ctggttacca aagtcggcac attctcttac gtccaacaat gcagacttta atttgtgatg 540 tacattcaat aacaagtgat aaccacaaat ggacccaggt tagttgtttt gttttttaat 600 ctcaaacagg caaaatatag gatgaaaaaa aattatcatt aagcaaaagt gattttctgc 660 ttatttttat tcaataatta agtttgatgc tttatgtgaa aagctggtat tcctttataa 720 gatctagaag ttaagggtct ctttatatgt gtagtaatcc ctcaagttgc ctaagatcat 780 tttaaggtca agctggccta atatattcaa tgagataaaa cttagttctt tatctcctct 840 caaacagaag aaaaatgttt tgtttttacc atggttacaa atagatactg gttttttttt 900 tttcaaataa ttcaagtttc taaaccctag cctagcctat ctttctttgc catttatact 960 ggttgccttg aaatgagggg aactctctta cccctgagaa taaccagtta acccctccag 1020 ttctggctca gtgttatatg aggggacttc agaaagtttg tggaaaactg gaattaaaag 1080 ataataataa aaaatataaa cttttcttct caatataagc tccatcaagt tcaagatgct 1140 tgtaaatgat atcaaccatt tatttagtcc acccctgaag aactgagggt cctgggaact 1200 gaaccatatc aatgcaatct tttctacatt attaactgaa gaaaaatggg tactttttaa 1260 actttttttt tttaagatta ggaaacaaaa agaagtcaga aggagccaaa tctggactgt 1320 aaggtgcata cctaatggtt tcccatcaaa actcttacaa aatttctctt ttttgatgag 1380 aggaatgagt agaggcattg tggtgcagaa gtctctagtg aagctttccc aggcattttt 1440 ctgccgaagc tttggctaac tttctcaaaa cactcataat aagcacgtta tcattctttg 1500 ttccttcaga aagtcaacaa gcaaaatgtc ttgagcatcc cagaaaactg tttccatgat 1560 ctttgctctt catctgtctg cttttgcttt gactgaatca cttctgcctc ttggtggcca 1620 ttgccttaat tgtgctttac tatcttcagg attatactgg aaagaatgct ttagtatctt 1680 ggtcctactt gttgaaaatt tctattgaaa gctctgcttt tgcagctgat cgggatgcag 1740 tggttttggt acccatcgag tggaaagttt actcaacttt aatttttcag tcaaaattgt 1800 tcaggctgaa ccagttgaga ggcctatagt gttggcaatt gtttctgctg ttaatcattg 1860 gtcctcttca gttaggttac aaacaaaatg aatttttttc ctcgtaaatt gatgtggaag 1920 atctgctgct gcaggcttcg tcttcaacat agtcttgtcc cttcttaaaa caagttaccc 1980 atttgtaaac tgctgctttc tttgaggcat tcttctcata aacttttcaa aaagcatcag 2040 tgatttcaca attcttccac tcaagcttca ccatcaattt gatgtttgtt cttgcttcag 2100 ttttagcaga attcctgttg ctctggtaaa ggctgttttc aaactgatgt cttatccttc 2160 ttagtgtttc aaactaggtt ctgttcagac atgttataac agcttagtac atgtttattt 2220 tggtgcaaaa agttttgaaa cctatgtata gttttttctt aatactcatt tttcataaac 2280 tttttaaaga ccccttgtat atgagatgtc cacttcacaa aagtgttcag ttgcctgact 2340 atagtgagga ataattacta agtcaaaaga aaatatcagt aatggtagtt atcctttctg 2400 tgacatgtga ttataaacta agcttcagtt catcagtaac taccaagtat tgtgttttgg 2460 tttgggctat aatgttgtca tctacaaaaa gattaaaagc tattaaaaga atattggaaa 2520 acagaaaaac tcattggtta ccatcagagt ttgctagggc atcagattct tactctgaag 2580 attgataaag gagagaatat aatatttatc ctgcccttct tgttatgaac tgtattttag 2640 gcagccaagt aactgaggga aaattcttag gaaaatttcc agctaatagg tgcaaaagaa 2700 atgatagact tttaaaaaat aaaagtttga aagtcttaat gaagtagtga atctagacag 2760 cagtatttct tggatgtgaa aaccattaga tgataggtta atgggaaatt ttataatgta 2820 gaaatctgat caaacccact gattgaagat gagacagtca attattgtgt acctcctggt 2880 ttgatgcaag agacagtaca caacagtagt aatagcacca ataaagaact cttgtccaaa 2940 aaaaaaaaaa aa 2952          <210> 773 <211> 1716 <212> DNA <213> Homo sapiens    <400> 773 gcgggtttct gcctcaggcc ctgccctgct ctactctgcg ctctctgccc gcgccgccgc 60 cgcctcagcc tcggccctgc gctgcgcgcc cggcccgtgc tgccatggcc tgccgcccgc 120 gaagcccgcc gaggcatcag agccgctgcg acggtgacgc cagcccgccg tcccccgcgc 180 gatggagcct gggacggaag cgcagagccg acggcaggcg ctggaggccc gaagacgccg 240 aggaggcaga gcaccgcggc gccgagcgca gacccgagag ctttaccact cctgaaggcc 300 ctaaaccccg ttccagatgc tctgactggg caagtgcagt tgaagaagat gaaatgagga 360 ccagagttaa caaagaaatg gcaagatata aaaggaaact cctcatcaat gactttggaa 420 gagagagaaa atcatcatca ggaagttctg attcaaagga gtctatgtct actgtgccgg 480 ctgactttga gacagatgaa agtgtcctaa tgaggagaca gaagcagatc aactatggga 540 agaacacaat tgcctacgat cgttatatta aagaagtccc aagacacctt cgacaacctg 600 gcattcatcc caagacccct aataaattta agaagtatag tcgacgttca tgggaccagc 660 aaatcaaact ctggaaggtg gctctgcatt tttgggatcc tccagcggaa gaaggatgtg 720 atttgcaaga aatacaccct gtagaccttg aatctgcaga aagcagctcc gagccccaga 780 ccagctctca ggatgacttt gatgtgtact ctggcacacc caccaaggtg agacacatgg 840 acagtcaagt ggaggatgag tttgatttgg aagcttgttt aactgaaccc ttgagagact 900 tctcagccat gagctaactg ccccctggcg gccaggaaga gaaacagctc ctccccgact 960 aggtggaagg ctggccaggc accaagcatg tgtgtgcact tgtacctggt ggtttctctg 1020 ttagcagtcc attagctcat gctgaattat ttttgcctta ctttcttaag aaacattaat 1080 tttatgtata gtgagtatat tttgcatgtt ttaaattgta aatggagcta agtccaagaa 1140 agtacttgaa gctctcttcc agcgagctta attgcgtaat ccctgttgtc ctccagggta 1200 agctgacacg tctacataac tggttttcca caggcatctt cagttattgc ttgtcaggtg 1260 gactgttttg gatttaacca tgtaatccat gggaccaatt gagagtcagc tacttttata 1320 ggcatcaaag tattctcaga cacctttaat atctttatgg aaacttaatt tttggccttt 1380 tatcaatatg tcataacagc attctgaagt cagacattgt taaattgagc tattaaacta 1440 atgagtttta tgtaagttat atggtcttaa tttggtactt gtaaatagca ctagttagac 1500 tctttagaat actccaagag ttagggcagc agagtggagc gatttagaaa gaacatttta 1560 aaacaatcag ttaatttacc atgtaaaatt gctgtaaatg ataatgtgta cagattttct 1620 gttcaaatat tcaattgtaa acttcttgtt aagactgtta cgtttctatt gcttttgtat 1680 gggatattgc aaaaataaaa aggaaagaac cctctt 1716       <210> 774 <211> 2004 <212> DNA <213> Homo sapiens    <400> 774 cgatcttttt acaaaattag agaagcaagt agtatggtga ttggcaggaa tttctcagat 60 ttgaatcaag ttctgatgtt aaaatggaag attctgttta aagcttgtat tttcaaggaa 120 tacttataaa catttttatc aggcatcttc ctgtttctct taaatacttc cttttttgac 180 ttaaaaatgt tagccagtga atgcttgaca aatttgtgtt tttgtccttt tcagttgtca 240 ctcagcccag tccatcagtt tctcagccca gtacttctca gagtgaagaa aaagctcctg 300 aattgcccaa accaaagaaa aacagatgtt tcatgtgcag aaagaaagtt ggtcttacag 360 ggtttgactg ccgatgtgga aatttgtttt gtggacttca ccgttactct gacaagcaca 420 actgtccgta tgattacaaa gcagaagctg cagcaaaaat cagaaaagag aatccagttg 480 ttgtggctga aaaaattcag agaatataaa ttacttcttg tgaagagact gaaactttgt 540 ttttatttta atatatcgta ggaaaacatt aaagagcaga tgcatggcca tttttctttg 600 atgttctcca gagttttaca ttacacttgt ctgtcttata attgatattt taggatgttt 660 gggtgtttgt tacaggcaga attggataga tacagcccta caaatgtata tgccctcccc 720 tgaaaaaaat tggatgaaaa tctgcacagc aaagtgaaac acacagataa taggaacaaa 780 atgtagttcc catgtgccaa acaaaataaa tgaaatctct gcatgtttgc agcatatctg 840 ccttttggga atgtaatcaa ggtataatct ttggctagtg ttatgtgcct gtattttttt 900 aaaatggtac accagaaaag gactggcagt ctacttctac catagttaaa cttcaccctc 960 tttaatttca caacatattc tttggaagca ggaagaaatg ctcataaaga ggatcagacc 1020 ttctttcccg tgaaaccagt atttggcgcc atatataagc ctggttaaat tggtcatcta 1080 aagctgtcaa ataagacatt ctgtgaaagg taaacatcga aactggttat aagtaaaacc 1140 atcaagccaa caacagggtc ttgagataac ctttgaagct tattgtactg gcctgcacca 1200 gaagatgtct gcattactca ttgctaaaaa tgtgtagcac agaactgcac taggattaat 1260 ttgtttacaa gaagaaattt aaactctacg tttggttttc acatacagca gctctattga 1320 ataacatgca tctgaatttt aagttgcaaa ggtatctgaa taatttttca tgtgcatctt 1380 ttgtcgaatg ttttggttca agaaagaatg tttaaagctt tttaaaagac ttcagttctt 1440 aatgtaactg tacccttctg catggaaaat cataaccaac atggctgcag tagacttctt 1500 agtggtatcc agcgccactt gcagagggct gctttatcat attgtacttg ggtgtaggac 1560 tctagtgttc ttgggtgtat tgcatgggct gcattatcta cagcattgta caataacaac 1620 tagaaaaggc agtatacttc actgatgctt gtctggtaat aatcacttct gtgttataat 1680 ggaaggtttt ttgtgatgta tgaaacttgt gttttttata tataaatgag tatagttagt 1740 gttgtggtaa tgcctgtttt catctgtaaa tagttaagta tgtacacgag gcactacttc 1800 tgatttattg caatgttcag tcctagtttt tacttttatt cttaaagcat tcagttttgc 1860 tttcaatttt atgtacctta gttctgagtt agacctgcag atgtgtacag atagttcata 1920 tttatgtatt gcacataatc atgctattca gcattgatgc tatattgtat tatgtaaata 1980 ataaaagcca tgtacagagg gaaa 2004

[0097]

[Brief description of drawings]

FIG. 1 GK-CTL (HLA-A2402 / A02
FIG. 06) shows that HLA-A24-restricted tumor cells are recognized and IFN-γ is produced.

[Fig. 2] A tumor antigen encoded by a tumor antigen gene clone 5 (MRP3) obtained from a human lung cancer cell line 11-18 was recognized by GK-CTL in an HLA-A2402 restricted and dose-dependent manner, and its IFN was recognized. FIG. 7 is a diagram showing that γ production is promoted.

FIG. 3 shows that the tumor antigen encoded by clone 114, which is a tumor antigen gene obtained from human lung cancer cell line 11-18,
It is a figure which shows being recognized by GLA-A2402 HLA-A2402 restrictively and dose-dependently, and promoting its IFN-gamma production.

FIG. 4 shows that the tumor antigen encoded by clone 50, which is a tumor antigen gene obtained from human lung cancer cell line 11-18, is G
It is a figure which shows that HLA-A2402 is restricted and dose-dependently recognized by K-CTL to promote its IFN-γ production.

FIG. 5 shows that the tumor antigen encoded by clone 83, which is a tumor antigen gene obtained from human lung cancer cell line 11-18, is G
It is a figure which shows that HLA-A2402 is restricted and dose-dependently recognized by K-CTL to promote its IFN-γ production.

FIG. 6 shows that the tumor antigen encoded by clone 111, which is a tumor antigen gene obtained from human lung cancer cell line 11-18,
It is a figure which shows being recognized by GLA-A2402 HLA-A2402 restrictively and dose-dependently, and promoting its IFN-gamma production.

FIG. 7 shows that the tumor antigen encoded by clone 96, which is a tumor antigen gene obtained from human lung cancer cell line 11-18, is G
It is a figure which shows that HLA-A2402 is restricted and dose-dependently recognized by K-CTL to promote its IFN-γ production.

FIG. 8 shows that the tumor antigen encoded by clone 122, which is a tumor antigen gene obtained from human lung cancer cell line 11-18, is
It is a figure which shows being recognized by GLA-A2402 HLA-A2402 restrictively and dose-dependently, and promoting its IFN-gamma production.

FIG. 9: Tumor antigen gene clone 5 (MRP
The tumor antigen peptide derived from the gene product of 3) is GK-C.
It is a figure which is recognized by TL and promotes the IFN-gamma production.

FIG. 10: Tumor antigen peptide derived from the gene product of the tumor antigen gene, clone 114 or clone 19-5-114, was recognized by GK-CTL and its IFN-
It is a figure which shows promoting γ production.

FIG. 11 is a diagram showing that a tumor antigen peptide derived from the gene product of the tumor antigen gene, clone 50, is recognized by GK-CTL and promotes its IFN-γ production.

FIG. 12 is a diagram showing that the tumor antigen peptide derived from the gene product of the tumor antigen gene, clone 83, is recognized by GK-CTL and promotes its IFN-γ production.

FIG. 13 shows that the tumor antigen peptide derived from the gene product of clone 111, which is a tumor antigen gene, is recognized by GK-CTL and promotes its IFN-γ production.

FIG. 14: Tumor antigen gene clone 96 (HB
The tumor antigen peptide derived from the gene product of P) is GK-C.
It is a figure which is recognized by TL and promotes the IFN-gamma production.

FIG. 15: Tumor antigen gene clone 122 (Z
The tumor antigen peptide derived from the gene product of FN) is GK-
It is a figure which shows being recognized by CTL and promoting its IFN-gamma production.

FIG. 16: Tumor antigen peptide 5-503 (MRP3-
503) is recognized by GK-CTL in a peptide dose-dependent manner and promotes its IFN-γ production.

FIG. 17: Tumor antigen peptide 5-692 (MRP3-
692) is recognized by GK-CTL in a peptide dose-dependent manner and promotes its IFN-γ production.

FIG. 18: Tumor antigen peptide 5-765 (MRP3-
765) is recognized by GK-CTL in a peptide dose-dependent manner and promotes its IFN-γ production.

FIG. 19: Tumor antigen peptide 5-1293 (MRP3
-1293) is recognized by GK-CTL in a peptide dose-dependent manner and promotes its IFN-γ production.

FIG. 20 shows that the tumor antigen peptide 114-1-275
It was recognized by GK-CTL in a peptide dose-dependent manner, and its I
It is a figure which shows that FN-γ production is promoted.

FIG. 21: Tumor antigen peptide 114-3-54 was recognized by GK-CTL in a peptide dose-dependent manner, and its IF
It is a figure which shows promoting N-gamma production.

FIG. 22: Tumor antigen peptide 50-1-767 was recognized by GK-CTL in a peptide dose-dependent manner, and its IF
It is a figure which shows promoting N-gamma production.

FIG. 23. Tumor antigen peptide 50-2-383 was recognized by GK-CTL in a peptide dose-dependent manner, and its IF
It is a figure which shows promoting N-gamma production.

FIG. 24 is a diagram showing that PBMC derived from a lung cancer patient incubated with a tumor antigen peptide recognizes cells pulsed with each corresponding peptide and promotes IFN-γ production.

FIG. 25 is a diagram showing that PBMC derived from a lung cancer patient incubated with a tumor antigen peptide recognizes 11-18 lung cancer cells (HLA-A24 ⁺ ) and promotes IFN-γ production.

FIG. 26 is a diagram showing the amount of IFN-γ production when PBMC derived from a healthy person that had been incubated with a tumor antigen peptide was used as an effector cell, and cells corresponding to each peptide were pulsed as a target cell.

FIG. 27: Tumor antigen peptide is PB derived from lung cancer patient
It is a figure which shows that HLA-A24 restricted tumor specific cytotoxic T cell can be induced from MC. In the figure, the solid line indicates cytotoxicity against 11-18 lung cancer cells (HLA-A24 ⁺ ), and the broken line indicates QG56 lung cancer cells (HLA-A2).
4 ⁻ ).

FIG. 28. Tumor antigen peptide (MRP3-503, M
RP3-692, MRP3-765, or MRP3-
1293) and P from lung cancer patients
BMC recognizes Sq-1 lung cancer cells (HLA-A24 ⁺ ) or cells pulsed with the corresponding peptides to recognize IF
Promoting N-γ production (FIG. A), and that PBMC incubated with the peptide specifically recognizes the peptide and enhances IFN-γ production (FIG. B)
FIG.

FIG. 29. Tumor antigen peptide (MRP3-503, M
RP3-692, MRP3-765, or MRP3-
1293), PBMC obtained from 3 lung cancer patients, 4 renal cancer patients, and 2 colon cancer patients pulsed with the same peptide as each peptide used for stimulation (FIG. A) and / or Sq-1 lung cancer cells (HLA-A
24 ⁺ ) (FIG. B) and recognizes that IFN-γ production is promoted.

FIG. 30. Tumor antigen peptide (MRP3-503, M
RP3-692, MRP3-765, or MRP3-
1293) can induce HLA-A24-restricted tumor-specific cytotoxic T cells from PBMCs of lung cancer patients or renal cancer patients, Sq-1 lung cancer cells and / or 11-18 lung cancer cells (A figure). ), Or MRP3-50
3 or MRP3-765 pulsed cells (Fig. B)
It is a figure which shows the cytotoxicity with respect to. In A Figure, QG56 lung cancer cells (HLA-A24 ^-) is a negative control. In Figure B, HIV means negative control peptide, 765 and 503 means cells pulsed with each peptide, and no peptide means cells not pulsed with peptide.

FIG. 31. Tumor antigen peptide (MRP3-692, M
FIG. 8 shows that recognition of tumor cells by CTLs induced from PBMCs derived from lung cancer patients by stimulation with RP3-765 or MRP3-1293 is associated with MRP3 expression in the tumor cells (FIG. A). . Figure B is originally MRP
To Caki-1 renal cancer cells with low expression of MRP3-69
FIG. 2 shows that pulsed 2 is recognized by CTL induced by stimulation of MRP3-692.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61P 35/00 C07K 14/47 4C084 C07K 14/47 16/30 4C085 16/30 C12N 1/15 4C087 C12N 1 / 15 1/19 4H045 1/19 1/21 1/21 C12P 21/02 C 5/10 C12Q 1/68 Z C12P 21/02 G01N 33/15 Z C12Q 1/68 33/50 Z G01N 33/15 33 / 53 D 33/50 M 33/53 33/566 33/574 33/566 C12N 15/00 ZNAA 33/574 5/00 AF Term (reference) 2G045 AA25 AA40 BA11 BB50 DA12 DA13 DA14 DA36 FB02 FB03 4B024 AA01 AA11 BA36 CA04 CA09 CA20 DA02 DA03 EA04 GA13 HA11 HA13 HA14 HA17 4B063 QA01 QA05 QQ21 QQ41 QQ43 QQ53 QQ79 QQ89 QR08 QR32 QR35 QR40 QR42 QR56 QR62 QR77 QR80 QS16 QS25 QS31 QS34 QX02 QX10 4B064 DA05 CA14 CA31 CA01 CA14 CA05 4B065 AA01X AA58X AA72X AA90X AA93Y AA94X AB01 AC14 BA02 BA05 BA30 BD50 CA24 CA45 CA46 4C084 AA13 NA14 ZB262 4C085 AA03 BB31 CC03 CC22 DD62 4C087 BC75 CA83 CA12 NA14 ZB26 4H045 DA75 FA71 FA20 CAABA BA30 BA50 BA30 BA50

Claims (21)

[Claims] 1. SEQ ID NO: 1 to SEQ ID NO: 766 in the sequence listing
A peptide comprising the amino acid sequence according to any one of 1. 2. SEQ ID NO: 1 to SEQ ID NO: 766 in the sequence listing
A pharmaceutical comprising a peptide comprising the amino acid sequence according to any one of 1. 3. SEQ ID NO: 1 to SEQ ID NO: 766 in the sequence listing
A cancer vaccine comprising a peptide consisting of the amino acid sequence according to any one of 1. 4. The method according to claim 2, which is used for treating lung cancer or renal cancer.
Or the pharmaceutical or cancer vaccine according to 3. 5. SEQ ID NO: 1 to SEQ ID NO: 766 in the sequence listing
An inducer of cytotoxic T cells, which comprises a peptide consisting of the amino acid sequence according to any one of 1. 6. SEQ ID NO: 1 to SEQ ID NO: 766 in the sequence listing
A method for inducing cytotoxic T cells, which comprises using the peptide consisting of the amino acid sequence described in any one of 1. 7. SEQ ID NO: 1 to SEQ ID NO: 766 in the sequence listing
A polynucleotide encoding a peptide comprising the amino acid sequence according to any one of 1 to 6 or a complementary strand thereof. 8. SEQ ID NO: 1 to SEQ ID NO: 766 in the sequence listing
A polynucleotide encoding a peptide comprising the amino acid sequence according to any one of 1 to 3, which is the polynucleotide according to any one of SEQ ID NO: 767 to SEQ ID NO: 774 or a complementary strand thereof. 9. The polynucleotide according to any one of SEQ ID NOs: 767 to 774, wherein the polypeptide encoded by the polynucleotide induces cytotoxic T cells and / or cytotoxic T cells. A polynucleotide or its complementary strand that is recognized by. 10. A polynucleotide which hybridizes with the polynucleotide according to any one of claims 7 to 9 or a complementary strand thereof under stringent conditions. 11. A recombinant vector containing the polynucleotide according to any one of claims 7 to 10 or a complementary strand thereof. 12. The recombinant vector according to claim 11, wherein the recombinant vector is an expression recombinant vector. 13. A transformant into which the recombinant vector according to claim 11 or 12 is introduced. 14. The method for producing the peptide according to claim 1, comprising a step of culturing a transformant into which the recombinant vector according to claim 12 has been introduced. 15. An antibody that immunologically recognizes the peptide according to claim 1. 16. At least HLA- interacting with the peptide according to claim 1 and / or HLA-A24.
A compound that enhances recognition of the peptide by an A24-restricted cytotoxic T cell, and / or interacts with the polynucleotide according to any one of claims 7 to 10 or its complementary strand to enhance its expression. A method for identifying a compound, comprising the peptide according to claim 1, the polynucleotide according to any one of claims 7 to 10 or a complementary strand thereof, the recombinant vector according to claim 11 or 12, The transformant according to claim 13, or claim 1.
A method comprising using at least one of the antibodies according to claim 5. 17. A compound obtainable by the method of claim 16. 18. A compound that enhances recognition by HLA-A24 restricted cytotoxic T cells for at least one of the peptides of claim 1, or claims 7-10.
A compound which interacts with the polynucleotide according to any one of the items 1 to 3 or a complementary strand thereof to enhance its expression. 19. The peptide according to claim 1, claim 7.
A polynucleotide according to any one of claims 1 to 10 or a complementary strand thereof, a recombinant vector according to claim 11 or 12, a transformant according to claim 13, an antibody according to claim 15, and a claim. A pharmaceutical composition for treating cancer, which comprises at least one of the compounds according to 17 or 18. 20. A method for quantitatively or qualitatively measuring the peptide according to claim 1 or the polynucleotide according to any one of claims 7 to 10. 21. A reagent kit used in the method according to claim 16 or 20, wherein the peptide according to claim 1, the polynucleotide according to any one of claims 7 to 10, and the polynucleotide according to claim 11. Or the recombinant vector according to claim 12, the transformant according to claim 13, or claim 1.
A reagent kit comprising at least one antibody according to item 5.