WO1996012190B1 - Presentation of hydrophobic antigens to t-cells by cd1 molecules - Google Patents
Presentation of hydrophobic antigens to t-cells by cd1 moleculesInfo
- Publication number
- WO1996012190B1 WO1996012190B1 PCT/US1995/013274 US9513274W WO9612190B1 WO 1996012190 B1 WO1996012190 B1 WO 1996012190B1 US 9513274 W US9513274 W US 9513274W WO 9612190 B1 WO9612190 B1 WO 9612190B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- cdl
- presented
- antigen
- lipoarabinomannan
- lipoarabinomannan antigen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
Abstract
Provided are CD1 presented antigens, compositions, cells, inhibitors and methods relating to the use of lipoarabinomannan (LAM) antigen presentation by CD1 molecules, including: methods for detecting the presence of a CD1-presented LAM antigen in a sample; methods for isolating such CD1-presented LAM antigens and the isolated antigens; vaccines containing CD1-presented LAM antigens and vaccination methods; methods of blocking CD1 LAM antigen presentation; methods of identifying and/or isolating CD1 blocking agents and the isolated CD1 blocking agents; methods of inducing CD1 expression; and T-cells for use in the methods disclosed herein.
Claims
1. A method for producing a vaccine containing a CDl- presented lipoarabinomannan antigen comprising the steps of: a) incubating a sample containing a CDl-presented lipoarabinomannan antigen with CDl-positive cells; b) separating said CDl-positive cells displaying CDl-bound lipoarabinomannan antigen from said sample; c) separating the CDl-presented lipoarabinomannan antigen from said CDl-positive cells displaying said antigen; and d) formulating said separated CDl-presented lipoarabinomannan antigen so as to form a vaccine.
2. A method of producing a vaccine containing a CDl- presented lipoarabinomannan antigen comprising the steps of: (a) fractionating a sample containing a CDl-presented lipoarabinomannan antigen into two or more fractions; (b) testing said fractions for the presence of a CDl- presented antigen; and (c) formulating one or more fractions which contains said CDl-presented lipoarabinomannan antigen so as to form a vaccine. 81
3. The method of Claim 1 or Claim 2 wherein:
(a) said CDl-presented lipoarabinomannan antigen is presented by a CDl molecule selected from the group consisting of CDla, CDlb, CDlc, CDld and CDle; or
(b) said CDl-presented lipoarabinomannan antigen is isolated from a Mycobacterial species selected from the group consisting of M. tuberculosis, M. bovis, M. leprae, M. fortui tum and M. avium .
4. A vaccine containing a CDl-presented lipoarabinomannan antigen producible by a method according to any one of Claims 1 to 3.
5. Use of a CDl-presented lipoarabinomannan antigen for the manufacture of a medicament which induces a specific T cell response, said medicament for use in vaccination.
6. A vaccine which induces a specific T cell response in a vertebrate upon administration to said vertebrate, the vaccine comprising: (a) an effective specific T cell-inducing amount of a CDl-presented lipoarabinomannan antigen or a functional fragment or analog thereof and a pharmaceutically acceptable carrier; or (b) an effective specific T cell-inducing amount of a CDl-presented lipoarabinomannan antigen or a functional fragment or analog thereof, complexed with a CD1+ molecule, and a pharmaceutically acceptable carrier 82
7. A vaccine according to Claim 6 further comprising:
(a) one or more cyto ines or other molecules which induce CDl expression on antigen-presenting cells; or (b) one or more different antigens; or
(c) a CDl molecule selected from the group consisting of CDla, CDlb, CDlc, CDld and CDle, wherein said vaccine comprises an antigen:CDl complex.
8. The vaccine of Claim 7, wherein at least one of the different antigens is a non-CDl presented antigen which is selected from an MHC-I presented antigen or an MHC-II presented antigen.
9. A method for vaccination, comprising the step of administering a vaccine according to Claim 6, 7 or 8 in an amount effective to provide an immune response to said lipoarabinomannan antigen in a bird or mammal.
10. A method according to claim 9, wherein said vaccine is administered orally or parenterally.
11. Use of a CDl-presented lipoarabinomannan antigen (or its functional equivalent) for the manufacture of a medicament for enhancing the immunity of a vertebrate by inducing a specific T cell response. 8 3
12. Use of (a) a CDl-presented lipoarabinomannan antigen
(or its functional equivalent) and (b) one or more additional non-specific response inducing components for the manufacture of a medicament for enhancing the immunity of a vertebrate by inducing a specific T cell response and said non-specific response.
13. A vaccine according to Claim 6, wherein the lipoarabinomannan antigen is:
(a) a cellular component of an organism; or (b) derived from a bacterial, fungal, or protozoan cell.
14. A method for enhancing or accelerating the immunity of a vertebrate which comprises administering to the vertebrate an effective immunizing amount of a vaccine comprising a CDl-presented hydrophobic antigen or its functional equivalent.
15. A CDl-blocking agent for use in therapy which inhibits CDl-restricted lipoarabinomannan antigen presentation selected from the group consisting of an antibody, a synthetic peptide, an inhibitor of CDl-restricted lipoarabinomannan antigen presentation, and an lipoarabinomannan antigen antagonist derived from a CDl-presented antigen.
16. A method for inhibiting CDl-restricted lipoarabinomannan antigen presentation by CDl-positive cells comprising the step of contacting cells displaying a CDl molecule with the CDl blocking agent of Claim 15. 8 4
17. A method for detecting a CDl-presented lipoarabinomannan antigen in a sample comprising the steps of:
(a) contacting said sample with CDl positive cells; (b) contacting said CDl positive cells with T cells; and (c) measuring the proliferative or cytolytic response of said T cells.
18. A method for isolating a CDl-presented lipoarabinomannan antigen from a sample comprising the steps of :
(a) incubating said sample with CDl positive cells which bind said CDl-presented lipoarabinomannan antigen, in order to generate CDl positive cells displaying CDl-bound lipoarabinomannan antigen;
(b) separating said CDl positive cells displaying CDl-bound lipoarabinomannan antigen from said sample; and
(c) separating the CDl-presented lipoarabinomannan antigen from said CDl-positive cells displaying said lipoarabinomannan antigen.
85
19. An isolated CDl-presented lipoarabinomannan antigen producible by a method comprising the steps of:
(a) incubating a sample with CDl positive cells which bind said CDl-presented lipoarabinomannan antigen,, in order to generate CDl-positive cells displaying CDl-bound lipoarabinomannan antigen;
(b) separating said CDl positive cells displaying CDl-bound lipoarabinomannan antigen from said sample; and (c) separating the CDl-presented lipoarabinomannan antigen from said CDl positive cells displaying said antigen.
20 An isolated T-cell that recognizes a CDl-presented lipoarabinomannan antigen.
21. A T-cell according to claim 20, wherein said CDl- presented lipoarabinomannan antigen is: (a) presented by a CDl molecule selected from the group consisting of CDla, CDlb, CDlc, CDld and CDle; (b) is isolated from a Mycobacterial species selected from the group consisting of M. tuberculosis, M. bovis , M. leprae, M. fortui tum and M. avium .
8 6
22. A method for providing a T-cell according to claim 20, comprising the steps of :
(a) purifying T-cells which are capable of binding a CDl-presented lipoarabinomannan antigen from a sample containing T-cells,•
(b) incubating a mycobacterium with CD1+ cells which bind said CDl-presented lipoarabinomannan antigen to generate CD1+ cells displaying said CDl- presented lipoarabinomannan antigen; (c) contacting the CD1+ cells displaying said CDl- presented lipoarabinomannan antigen of (b) with the T-cells of (a) ; and (d) isolating T-cells that recognize an isolated CDl- presented lipoarabinomannan antigen and give a proliferative response during step (c) , wherein said proliferative response does not occur in the presence of antibodies to CDl.
Priority Applications (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP95941326A EP0786088B1 (en) | 1994-10-13 | 1995-10-13 | Presentation of lipoarabinomannan antigens to t-cells by cd1 molecules |
| AU42779/96A AU694299B2 (en) | 1994-10-13 | 1995-10-13 | Presentation of hydrophobic antigens to T-cells by CD1 molecules |
| DE69525058T DE69525058D1 (en) | 1994-10-13 | 1995-10-13 | PRESENTATION OF LIPOARABINOMANNAN ANTIGENS TO T CELLS BY CD1 MOLECULES |
| JP8513411A JPH10510142A (en) | 1994-10-13 | 1995-10-13 | Presentation of hydrophobic antigen to T cells by CD1 molecule |
| AT95941326T ATE212129T1 (en) | 1994-10-13 | 1995-10-13 | PRESENTATION OF LIPOARABINOMANNAN ANTIGENS TO T CELLS BY CD1 MOLECULES |
Applications Claiming Priority (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/322,979 | 1994-10-13 | ||
| US08/322,980 US5679347A (en) | 1992-12-10 | 1994-10-13 | Methods of isolating CD1-presented antigens, vaccines comprising CD1-presented antigens, and cell lines for use in said methods |
| US08/322,980 | 1994-10-13 | ||
| US08/322,979 US5853737A (en) | 1992-12-10 | 1994-10-13 | Method for inducing a CD1-restricted immune response |
| US50149195A | 1995-07-12 | 1995-07-12 | |
| US08/501,600 | 1995-07-12 | ||
| US08/501,600 US6238676B1 (en) | 1992-12-10 | 1995-07-12 | Presentation of hydrophobic antigens to T-cells by CD1 molecules |
| US08/501,491 | 1995-07-12 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| WO1996012190A2 WO1996012190A2 (en) | 1996-04-25 |
| WO1996012190A3 WO1996012190A3 (en) | 1996-06-27 |
| WO1996012190A9 WO1996012190A9 (en) | 1996-08-01 |
| WO1996012190B1 true WO1996012190B1 (en) | 1996-09-06 |
Family
ID=27502254
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1995/013274 Ceased WO1996012190A2 (en) | 1994-10-13 | 1995-10-13 | Presentation of hydrophobic antigens to t-cells by cd1 molecules |
Country Status (7)
| Country | Link |
|---|---|
| EP (2) | EP0786088B1 (en) |
| JP (1) | JPH10510142A (en) |
| AT (1) | ATE212129T1 (en) |
| AU (1) | AU694299B2 (en) |
| CA (1) | CA2202680A1 (en) |
| DE (1) | DE69525058D1 (en) |
| WO (1) | WO1996012190A2 (en) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7063844B2 (en) | 1992-12-10 | 2006-06-20 | The Brigham And Women's Hospital, Inc. | Presentation of hydrophobic antigens to T-cells by CD1 molecules |
| US6238676B1 (en) | 1992-12-10 | 2001-05-29 | Brigham And Women's Hospital | Presentation of hydrophobic antigens to T-cells by CD1 molecules |
| WO1995028642A1 (en) | 1994-04-14 | 1995-10-26 | Brown, Keith, Edwin, Frank | A method for detecting the presence of a mycobacterium species and a kit and antibodies for use therein |
| JP2001515868A (en) * | 1997-09-12 | 2001-09-25 | ブライハム アンド ウイメンズ ホスピタル | Synthetic antigens for CD1 restricted immune response |
| JP2002511421A (en) * | 1998-04-13 | 2002-04-16 | ザ ブライハム アンド ウイミンズ ホスピタル， インコーポレイテッド | Vaccine composition comprising CD-1 antigen and T cell stimulating compound and method of using the same |
| WO2001094949A2 (en) * | 2000-06-05 | 2001-12-13 | The Brigham And Women's Hospital, Inc. | Soluble cd1 compositions and uses thereof |
| FR2819724B1 (en) * | 2001-01-22 | 2005-05-13 | Inst Necker | MEANS FOR INDUCING AN IMMUNE RESPONSE TO POLYCHARIDIC BACTERIAL ANTIGENS AND PROTEIN STRUCTURES OF VIRUS CAPSIDS |
| WO2004093903A2 (en) | 2003-04-18 | 2004-11-04 | The Brigham And Women's Hospital, Inc. | Methods and compositions for immunomodulation using cd1 antigens |
| GB0708874D0 (en) * | 2007-05-08 | 2007-06-13 | Univ The Of Birmingham | Assay for detecting mycrobacterial infection |
| CN112805369A (en) | 2018-08-08 | 2021-05-14 | 南特生物公司 | Recombinant CD 1-restricted T cells and methods |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU1423892A (en) * | 1991-02-12 | 1992-09-07 | Colorado State University Research Foundation | Monoclonal antibodies directed towards mycobacterial antigens |
| AU1564592A (en) * | 1991-02-12 | 1992-09-07 | Dynagen, Inc. | Agglutination test for mycobacterial antigens in biological samples |
| CA2165786A1 (en) * | 1993-06-21 | 1995-01-05 | Steven A. Porcelli | Methods of isolating cd1-presented antigens, vaccines comprising cd1-presented antigens, and cell lines for use in said methods |
-
1995
- 1995-10-13 DE DE69525058T patent/DE69525058D1/en not_active Expired - Lifetime
- 1995-10-13 EP EP95941326A patent/EP0786088B1/en not_active Expired - Lifetime
- 1995-10-13 AU AU42779/96A patent/AU694299B2/en not_active Ceased
- 1995-10-13 JP JP8513411A patent/JPH10510142A/en not_active Ceased
- 1995-10-13 CA CA002202680A patent/CA2202680A1/en not_active Abandoned
- 1995-10-13 EP EP01202176A patent/EP1170592A1/en not_active Withdrawn
- 1995-10-13 WO PCT/US1995/013274 patent/WO1996012190A2/en not_active Ceased
- 1995-10-13 AT AT95941326T patent/ATE212129T1/en not_active IP Right Cessation
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