Lukacher A E, Ma Y, Carroll J P, Abromson-Leeman S R, Laning J C, Dorf M E, Benjamin T L
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Exp Med. 1995 May 1;181(5):1683-92. doi: 10.1084/jem.181.5.1683.
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.
某些近交系小鼠携带的显性基因赋予其对多瘤病毒诱导肿瘤的易感性。这个基因，命名为Pyvs，是在高度易感的C3H/BiDa品系与高度抗性但H-2k相同的C57BR/cdJ品系之间的杂交中定义的。C57BR/cdJ小鼠的抗性可通过辐射克服，表明其具有免疫学基础。在F1与C57BR/cdJ回交小鼠中，肿瘤易感性与Mtv-7共分离，Mtv-7是C3H/BiDa品系携带的一种小鼠乳腺肿瘤前病毒。这表明Pyvs可能编码Mtv-7超抗原（SAG），并通过消除携带特定Vβ结构域的T细胞来消除多瘤肿瘤免疫监视。对110只回交小鼠的DNA分型显示，Pyvs与Mtv-7之间没有重组的证据。在C57BR/cdJ小鼠中，多瘤病毒特异性CD8+细胞毒性T淋巴细胞对Vβ6的强烈偏向性使用表明，携带这种Mtv-7 SAG反应性Vβ结构域的T细胞是体内关键的抗多瘤肿瘤效应细胞。这些结果表明Pyvs与Mtv-7 sag相同，并证明了一种基于内源性超抗原对宿主T细胞库的影响而导致对病毒诱导肿瘤的遗传性易感性的新机制。
