The general aim of my research is to develop the capacity to regulate or manipulate the cytolytic T lymphocyte (CTL) response. This interest extends to understanding the CTL response to viral infections, malignancies and also to alloantigens (because of the evidence for the involvement of CTLs in renal and bone marrow transplantation). In order to accomplish my more general goal I feel that is necessary to define on a molecular level, the antigenic requirements for triggering pre-CTLs and the antigens recognized by CTLs. Recent methodological advances have made it possible (1) to clone major histocompatibility complex (MHC) genes; (2) to isolate and purify MHC and viral antigens that retain CTL stimulating activity when inserted into artificial membranes or liposomes and (3) to clone helper T cells and CTLs. These monoclonal T cell lines provide a powerful probe to define the T cell recognition site(s) on MHC and viral antigens. Therefore, the specific aims of my research are as follows: (1) To utilize cloned MHC genes to define the antigenic sites on H-2 molecules recognized by allospecific and virus specific CTLs. Since there are likely to be multiple CTL recognition sites on these molecules, cloned allospecific and virus specific CTLs will be generated. (2) Cloned viral genes will be used to define the antigenic sites on viral proteins recognized by virus specific CTLs. Specifically, a cloned Mooney murine leukemia virus gp70 gene and a cloned influenza virus hemagglutinin (HA) gene will be manipulated to assess serological and CTL recognition sites. (3) Influenza viral proteins and H-2 proteins will be isolated and introduced into liposomes to study the antigenic requirements for triggering influenza virus specific CTLs. (4) Isolated H-2K/D and Ia antigens will be isolated and introduced into liposomes to define the antigenic requirements for triggering cloned T helper and T proliferating cells.
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