Host resistance to oncornavirus induced tumors is dependent on both T-cell-mediated and humoral antibody immune mechanisms. The experiments outlined in this proposal are designed to test the hypothesis that antibodies can regulate cellular and humoral immune responses to murine oncornaviral antigens through isotype and idiotype specific reactions. Immune responses of mice against Moloney-murine sarcoma virus (M-MuSV) infection and M- MuLV expressing lymphoma cells will be studied. Determination of the class and subclass of specific antibodies generated in response to Moloney sarcomas and lymphomas may reveal key information regarding why sarcomas regress in normal nonimmunized mice but lymphomas do not even though they share antigens. We have generated several hybridomas secreting monoclonal IgM antibodies that have specificity for an M-MuLV antigen expressed on the cell surface. The antibodies do not neutralize virus but can inhibit M-MuSV induced tumor growth in vivo. These monoclonal antibodies and newly generated IgG subclass monoclonal antibodies will also be tested for their ability to inhibit syngeneic lymphoma growth. Selected monoclonal antibodies have been used to generate hybridomas secreting monoclonal anti-idiotype antibodies (MAIDS). The MAIDS will be used to evaluate anti-idiotype regulation of immune responses to M-MuSV infection and M-MuLV induced tumors. Thus, we will attempt to modulate idiotype specific responses in animals in the presence and absence of virus induced tumor antigens by administering MAIDS or monoclonal antibodies with MuLV specificity. The monoclonal antibodies will also be used to search for idiotype or anti-idiotype positive T cells generated during an immune response to M-MuLV specific antigens. These studies should provide information that will be conceptually useful in our understanding of immunity to oncornavirus infection and suggest potential strategies for prevention or therapy of virus induced tumors.
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