The overall goal of these studies is to elucidate the cell surface moieties recognized by syngeneic cytotoxic T cells (CTL). Although significant progress has been made recently in identifying antigenic structures involved in the CTL response to infectious viruses, the virus-coded molecules recognized by CTL generated to cells transformed by oncogenic viruses have not been unequivocally identified in any system. Recent advances in the molecular biology of Simian virus 40 (SV4O) have allowed the production of mutant viruses that are unique and extremely powerful tools for studying immune recognition of SV4O-transformed cells. We will use these viruses, which produce a series of overlapping fragments of the SV4O T antigen, to analyze the immune response to this prototype """"""""transforming protein."""""""" Specifically, we will characterize the T antigen-like molecule found on the cell surface and investigate the mechanisms by which it is translocated to the plasma membrane. We will identify the portions of T antigen involved in CTL recognition to assess whether the response is to multiple determinants or to a dominant epitope and whether the recognition varies depending on the K or D molecule with which T is recognized. Finally, we will continue development of a model system for CTL recognition using a purified, well-characterized, small molecular weight membrane protein incorporated into the plasma membrane. This will allow analysis of the fine specificity of CTL not yet possible with the much larger T antigen. Together these studies will begin to dissect at a molecular level immune recognition of cell surface antigens with the ultimate goal of determining why some tumor-associated antigens elicit an effective antitumor immune response while others do not. (AG)
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