The present proposal is a continuation of our research into the pathogenesis and manipulation of adjuvant arthritis in Lewis rats using long-term lines and clones of T lymphocytes. Since the previous competitive reviewing we used clones A2b and A2c to probe expression libraries of MT antigens and discovered that both A2b and A2c recognized a 65KD protein of the BCG strains of MT. The epitope was identified as composed of 9 amino acids, position 180-188 in the sequence of the 65KD antigen. This sequence showed some homology with the link protein of cartilage proteolglycan. Thus we are in a position to identify the component of the joints cross-reactive with the MT nonapeptide. Immunization of Lewis rats with the purified 65KD protein induced resistance to subsequent attempts to trigger arthritis by immunization to whole MT in oil. We also succeeded in treating cells of clone A2b so that, similar to clone A2c, treated A2b could be used to vaccinate rats against adjuvant arthritis and to induce remission of established arthritis. Anti- idiotypic T cells were associated with resistance. The general aims of this proposal are to complete the characterization of the joint antigens recognized by clones A2b and A2c and by other functional T cell, and to elucidate the mechanism of resistance to arthritis induced by vaccination with such T cells.
The specific aims are as follows: 1. Characterization of Joint Target Antigens a. Synthetic peptides homologous with the nonapeptide. b. Monoclonal antibody t specific MT antigens c. Affinity purification of cross-reactive tissue antigens. 2. Characterization of Functional T cells a. Responses in active arthritis b. Development of additional lines and clones c. Anti-idiotypic antibody probes d. T cell receptor genes 3. Mechanisms of T Cell Vaccination a. Treatment of established arthritis b. Vaccines prepared from arthritic rats. c. Passive transfer of vaccinated state. d. Anti-idiotypic T cells e. Effects of responses to antigens 4. Inhibition of arthritis using T cell defined epitopes
| Cohen, I R (1992) Autoimmunity to hsp65 and the immunologic paradigm. Adv Intern Med 37:295-311 |
| Mor, F; Lohse, A W; Karin, N et al. (1990) Clinical modeling of T cell vaccination against autoimmune diseases in rats. Selection of antigen-specific T cells using a mitogen. J Clin Invest 85:1594-8 |
