Antigenic determinants in a virus-induced mouse mammary tumor recognized by cell-mediated immune assays

Purified tumor cell membrane (PTCM) fractions from spontaneous BALB/cfC3H mammary adenocarcinomas elicit blastogenic responses in spleen cells of tumor-bearing mice. Previous studies have demonstrated that splenic T-cells are the major responding cell population but have not clarified whether the antigens responsible for the reactions are exclusively viral in origin or may involve nonviral tumor-associated antigens (TAA). Pretreatment of PTCM preparations with polyvalent anti-murine mammary tumor virus (MuMTV) completely obliterated the ability of PTCM to stimulate an innocent bystander cytotoxicity reaction; however, it reduced the blastogenic response by only 60%, suggesting that the two assays may measure different antigenic reactivities. The specificity of the anti-MuMTV blocking for viral antigens was demonstrated by the complete absorption of the serum-blocking reaction with purified MuMTV particles in the cytotoxicity assay; however, absorption was only partial in the blastogenesis assay. Incubation with purified Rauscher murine leukemia virus particles failed to absorb the neutralizing effect of the sera. These data suggest that putative TAA can be detected in the blastogenesis assay but not in the cytotoxicity reaction. Ammonium sulfate-precipitated immunoglobulin fractions of sera from tumor-bearing BALB/cfC3H mice (TBMS) completely blocked the stimulatory potential of PTCM in both the blastogenesis and the cytotoxicity assays. In the reciprocal experiment to that described above, preabsorption of TBMS immunoglobulins with purified MuMTV completely removed the inhibition of the cytotoxicity but again only partially restored the blastogenic response. The reaction could be completely restored by preabsorption of TBMS with PTCM. These results support the contention of nonvirion antigen involvement in the blastogenesis reaction. In conclusion, these two assay systems detect different antigenic determinants on the MuMTV-expressing tumor cell membranes. Both viral and other antigens appear to be relevant in this model system, and serum factors present in the immunoglobulin fractions of tumor-bearing mice can inhibit T-cell responses directed at either kind of antigenic moieties.