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 susceptibility to tumors induced by polyoma virus. This gene, designated Pyvs, was defined in crosses between the highly susceptible C3H/BiDa strain and the highly resistant but H-2k-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 Pyvs might encode the Mtv-7 superantigen (SAG) and abrogate polyoma tumor immunosurveillance through elimination of T cells bearing specific V beta domains. DNA typing of 110 backcross mice showed no evidence of recombination between Pyvs and Mtv-7. Strongly biased usage of V beta 6 by polyoma virus-specific CD8+ cytotoxic T lymphocytes in C57BR/cdJ mice implicates T cells bearing this Mtv-7 SAG-reactive V beta domain as critical anti-polyoma tumor effector cells in vivo. These results indicate identity between Pyvs 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.
Lukacher
A E
AE
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Ma
Y
Y
Carroll
J P
JP
Abromson-Leeman
S R
SR
Laning
J C
JC
Dorf
M E
ME
Benjamin
T L
TL
D000818:Animals; D003433:Crosses, Genetic; D005260:Female; D008324:Mammary Tumor Virus, Mouse / Q000276:immunology* / Q000302:isolation & purification; D051379:Mice; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D030361:Papillomavirus Infections / Q000235:genetics / Q000276:immunology*; D011120:Polyomavirus; D011533:Proviruses / Q000302:isolation & purification; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D018089:Superantigens / Q000235:genetics / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014412:Tumor Virus Infections / Q000235:genetics / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens