Susceptibility to tumors induced by polyoma virus is conferred by an endogenous mouse mammary tumor virus superantigen

Abstract

A dominant gene carried in certain inbred mouse strains confers susceptibility to tumors induced by polyoma virus. This gene, designated Pyv(S), was defined in crosses between the highly susceptible C3H/BiDa strain and the highly resistant but H-2(k)-identical C57BR/cdJ strain. The resistance of C57BR/cdJ mice is overcome by irradiation, indicating an immunological basis. In F1 x C57BR/cdJ backcross mice, tumor susceptibility cosegregates with Mtv-7, a mouse mammary tumor provirus carried by the C3H/BiDa strain. This suggests that Pyv(S) might encode the Mtv-7 superantigen (SAG) and abrogate polyoma tumor immunosurveillance through elimination of T cells bearing specific Vβ domains. DNA typing of 110 backcross mice showed no evidence of recombination between Pyv(S) and Mtv-7. Strongly biased usage of Vβ6 by polyoma virus-specific CD8+ cytotoxic T lymphocytes in C57BR/cdJ mice implicates T cells bearing this Mtv-7 SAG- reactive Vβ domain as critical anti-polyoma tumor effector cells in vivo. These results indicate identity between Pyv(S) and Mtv-7 sag, and demonstrate a novel mechanism of inherited susceptibility to virus-induced tumors based on effects of an endogenous superantigen on the host's T cell repertoire.