H‐2 control of the cytotoxic antibody response against a newly defined MuLV‐related cell‐surface antigen: G (B10.A)

H‐2 ‐congeneic C57BL mice with milk transmission of B‐tropic murine leukemia virus (V+ mice) have a much higher lymphoma incidence than the same strains without milk‐transmitted virus (V—mice). Gene(s) within the major histocompatibility complex ( H‐2 ) influence virus titers, lymphoma incidence, lymphoma type and the anti‐MuLV envelope antibody response. In this paper, we report that the prevalence of cytotoxic antibodies to virus‐induced lymphomas is also regulated by the H‐2 complex. Milk transmission of MuLV resulted in the formation of cytotoxic antibodies against primary virus‐induced C57BL lymphomas. These antibodies detect an antigen that is also present on the RADAI tumor‐cell line, and on normal spleen cells of young adult B10.A ( H‐2 a ) mice of both V+ and V‐ sublines, but not on spleen cells of young adult B10 ( H‐2 b ) mice of either subline. These cytotoxic antibodies were detected in the sera of B10V+ and B10.A(5R)V+ animals, but not in the sera of B10.AV+ mice. This indicates that the prevalence of these antibodies is controlled by a gene in the K‐and/or I‐A region of the H‐2 complex. The presence of these cytotoxic antibodies in serum is recessively inherited. The specificity of the cytotoxic antibodies was investigated with a standard panel of transplantable tumor‐cell lines. Of these, only the RADAI cells expressed the target antigen in direct cytotoxicity tests and by absorption. The ability of B10V+ sera to lyse the B10.AV+ and RADAI tumor cells is ascribed to antibody activity against a new MuLV‐related cell‐surface protein: G (B10.A) . Immunochemical analysis and absorption experiments with different types of purified MuLV and MuLV‐infected cell lines indicate that the cytotoxic antibodies belong to low‐avidity IgM antibodies that are directed to MuLV.