Dependence of initiation of an innocent bystander cytotoxicity reaction on the association of viral antigens and tumor cell membranes in mice.

In chemically induced mouse mammary tumors in BALB/c mice, no murine mammary tumor virus (MuMTV) antigens could be detected in the tumor cell membranes. In contrast, in mammary tumors of spontaneous appearance in BALB/cfC3H mice neonatally infected with MuMTV, viral antigens could be detected by immunofluorescence. Specific activation of immune spleen lymphocytes in vitro by homologous tumor cell membrane preparations resulted in an innocent bystander cytotoxicity reaction in BALB/c mice bearing either the chemical- or virus-induced mammary tumors. Non-tumor bearers did not respond in this reaction. The cytotoxicity effector cell was a nylon-adherent Thy 1.2+, Lyt 1+, Lyt 2+ lymphocyte. Induction of the reaction in the chemically induced mammary tumor bearers was related to tumor-associated antigens, but in the mice with MuMTV-induced tumors, it was possible that all responses were solely due to viral antigens. Biochemical analyses using immunoprecipitation techniques indicated that the major external glycoprotein of MuMTV (gp52) was present in the tumor cell membrane preparations. Preincubation of the cell membranes of virus-induced tumors with anti-MuMTV completely blocked the capacity of this preparation to induce the cytotoxicity. Preabsorption of the anti-MuMTV with purified MuMTV removed all the blocking activity of these sera, indicating that the antigenic determinants recognized were of viral origin. However, purified MuMTV failed by itself to elicit the innocent bystander cytotoxicity. This observation indicates that an association with membranes was necessary for the viral antigens to initiate and/or effect this cell-mediated immune reaction.