RECOGNITION OF LEUKEMIA ANTIGEN BY ANTI-VIRAL CTL'S

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We propose to identify ways in which anti-viral CTL recognize or fail to recognize leukemia virus cell surface antigen in the murine system. In particular, we plan to study why normal cells from AKXL mice, which carry the Akv-1 murine leukemia provirus, are recognized by C57B1/6 anti-AKR/Gross virus CTL, whereas cells from other AKXL mice which carry the highly related Akv-4 provirus, are not recognized by such antiviral CTL's. Green and coworkers have used standard immunological techniques including CTL recognition and induction assays and antiviral monoclonal antibody recognition assays that clearly indicate the importance of the viral antigen gp70 in the CTL recognition process. To further study viral epitope expression for recognition by CTL, I propose here to clone and compare by restriction mapping the Akv-1 and Akv-4 proviral DNA loci. The cell surface viral antigens expressed by these proviruses and recognized by CTL will then be studied and compared by transfecting recombinant proviral subclones into fibroblast or lymphoblastoid cell lines. After culturing the transfected cells in G418 selective medium, viral antigen expression will be assayed for by cytofluorography using antiviral monoclonal antibodies and by CTL functional assays. By these means, we can better define the viral elements necessary for CTL recognition and induction and better understand the promotion of tumor establishment resulting from the failure of these processes.