SUSCEPTIBILITY TO TUMORS INDUCED BY POLYOMA-VIRUS IS CONFERRED BY AN ENDOGENOUS MOUSE MAMMARY-TUMOR VIRUS SUPERANTIGEN

A dominant gene carried in certain inbred mouse strains confers suscep tibility to tumors induced by polyoma virus. This gene, designated Pyv (S), was defined in crosses between the highly susceptible C3H/BiDa st rain and the highly resistant but H-2(k)-identical C57BR/cdJ strain. T he resistance of C57BR/cdJ mice is overcome by irradiation, indicating an immunological basis. In F1 x C57BR/cdJ backcross mice, tumor susce ptibility cosegregates with Mtv-7, a mouse mammary tumor provirus carr ied by the C3H/BiDa strain. This suggests that Pyv(S) might encode the Mtv-7 superantigen (SAG) and abrogate polyoma tumor immunosurveillanc e through elimination of T cells bearing specific V beta domains. DNA typing of 110 backcross mice showed no evidence of recombination betwe en Pyv(S) and Mtv-7. Strongly biased usage of V beta 6 by polyoma viru s-specific CD8(+) cytotoxic T lymphocytes in C57BR/cdJ mice implicates T cells bearing this Mtv-7 SAG-reactive V beta domain as critical ant i-polyoma tumor effector cells in vivo. These results indicate identit y between Pyv(S) and Mtv-7 sag, and demonstrate a novel mechanism of i nherited susceptibility to virus-induced tumors based on effects of an endogenous superantigen on the host's T cell repertoire.