The original goal of these studies was the detailed phenotypic and functional characterization of autoreactive T cells by the development and use of highly specific monoclonal antibodies and autoreactive T cell clones. Experiments thus far have provided evidence that T cells use the same subset-restricted glycoproteins as associative recognition elements for autologous MHC gene products as for allogeneic or virally transformed autologous stimulator cells. One novel aspect of these studies was the demonstration of the importance of Class I MHC-encoded molecules in autoreactivity. The data additionally indicated that the T3-Ti antigen receptor complex also has an important role in autologous T cell activation. A related group of studies have demonstrated the capacity of an antibody against a pan-T cell structure (that is not membrane-associated with the antigen-receptor complex) to modulate autoreactivity. The antibody can markedly enhance the autologous mixed lymphocyte reaction, function as a T cell mitogen, and cause modulation of its target membrane antigen from the T cell surface both in vitro and in vivo. Such modulation is associated with in vitro diminution in immune responsiveness. The goals for the remaining years of funding include development of new monoclonal antibodies that may serve to identify determinants that are enriched for or uniquely present on autoreactive T cells. These studies will use as immunogens both autoreactive T cell populations and lines, as well as autoreactive T cell clones developed in this phase of the study. The cells bearing such determinants and the structures themselves will be subjected to functional analysis, and the membrane structures will be biochemically characterized in detail. Structures that may represent autoreactive T cell antigen receptor idiotopes or isotypes will be a focus of further study, and their structural and molecular characterization will be of particular interest. These experiments should improve our understanding of physiologic T cell autoreactivity and may provide new and useful insights into the underlying mechanisms of autoimmune disease.
| Swack, J A; Mier, J W; Romain, P L et al. (1991) Biosynthesis and post-translational modification of CD6, a T cell signal-transducing molecule. J Biol Chem 266:7137-43 |
| Swack, J A; Gangemi, R M; Rudd, C E et al. (1989) Structural characterization of CD6: properties of two distinct epitopes involved in T cell activation. Mol Immunol 26:1037-49 |
| Gangemi, R M; Swack, J A; Gaviria, D M et al. (1989) Anti-T12, an anti-CD6 monoclonal antibody, can activate human T lymphocytes. J Immunol 143:2439-47 |
