The long term goal of the proposed research program is to understand immune functions of IL2-dependent and IL2-independent cytotoxic T cell precursors (pCTL). IL2-dependent and IL2-independent pCTL are defined by a rat anti-mouse monoclonal antibody, B4B2, which recognizes 50% of Lyt2+ cells. Isolation procedures have been established for Lyt2+B4B2+ (B4+) and Lyt2+B4B2-(B4-) T cells. Specifically, the following experiments will be carried out. 1. Characterization of the chemical structure of the B4b2 antigen by immunoprecipitation of radiolabeled cell surface antigens followed by polyacrylamide gel electrophoresis. Because the expression of B4B2 antigen is linked to a chromosomal region that codes for a major cluster of lymphoid differentiation antigens, knowledge of the structure of B4B2 antigen will help in establishing possible structural similarities and the function(s) of these closely linked lymphoid differentiation antigens. 2. Characterize immune functions of B4+ and B4- T cells. These include a) Cellular and lymphokine requirements for cell activation; b) induction of IL2 receptor expression; c) ability to produce IL2; d) Capacity for extended growth; e) Relative affinity between cytotoxic effector cells and targe cells; f) virgin vs primed T cells. These experiments will provide insights to why a drastically altered B4 antigen expression is found in autoimmune mice and perhaps establish the role(s) of B4+ T cells in controlling autoimmunity. 3. Determine the repertoire of pCTL from normal and athymic mice. The studies include a) Segregation of alloreactibe and self-reactive repertoires and b) Comparison of normal B4+ and B4- T cells with T cells found in nude mice. These studies might confirm and extend the already observed functional similarities between normal B4+ T cells and athymic T cells. If so, separation of Lyt2+ cells into B4+ and B4- will provide an experimental system to study the role of the thymus in the development of IL2-dependent and IL2- independent T cells.
