This is an application for study of cell-mediated immune responses to antigens encoded on the murine 17th chromosome outside, but adjacent to, the H-2 complex as traditionally defined. The major portion of this work will focus on gene products of the Qa-1/Tla region. These molecules, including the thymus leukemia antigen, appear most likely to function as differentiation antigens both in normal lymphocyte ontogeny and functional diversification of lymphocyte subsets, and in the development of T cell leukemias and lymphomas. We will extend our ongoing studies on H-2 nonrestricted T cell-mediated cytotoxic reactions induced by antigens of this region. A library of cytotoxic T cell clones with specificy for these determinants will be developed. Antigenic structures and polymorphisms recognized by cytotoxic T cells will be compared with those defined serologically with conventional and monoclonal antibodies. The role of H-2 genes in expression of Qa-1 antigens and in the control of cytotoxic T cell responses to Qa-1 will be defined. We will investigate regulation of T cell responses to Qa-1 antigens in autoimmune NZB mice and normal mice, with particular interest in defining physiological control processes. Receptor specificity for Qa-1 recognition by T cells will be compared with that for recognition for major histocompabitility complex antigens and for recognition of conventional antigens.
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