SUSCEPTIBILITY TO TUMORS INDUCED BY POLYOMA-VIRUS IS CONFERRED BY AN ENDOGENOUS MOUSE MAMMARY-TUMOR VIRUS SUPERANTIGEN
SUSCEPTIBILITY TO TUMORS INDUCED BY POLYOMA-VIRUS IS CONFERRED BY AN ENDOGENOUS MOUSE MAMMARY-TUMOR VIRUS SUPERANTIGEN
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DOI：
10.1084/jem.181.5.1683
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发表时间：
1995-05-01
影响因子：
15.3
通讯作者：
BENJAMIN, TL
中科院分区：
文献类型：
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作者：
LUKACHER, AE;MA, YP;BENJAMIN, TL
在某些近交系小鼠品系中携带的显性基因赋予对由多瘤病毒诱导的肿瘤的易感性。该基因命名为Pyv（S），在高度敏感的C3 H/BiDa菌株和高度抗性但H-2（k）相同的C57 BR/cdJ菌株之间的杂交中被定义。C57 BR/cdJ小鼠的抗性被照射克服，表明免疫学基础。在F1 x C57 BR/cdJ回交小鼠中，肿瘤易感性与Mtv-7共分离，Mtv-7是C3 H/BiDa株携带的小鼠乳腺肿瘤前病毒。这表明Pyv（S）可能编码Mtv-7超抗原（SAG），并通过消除携带特异性V β结构域的T细胞来消除多瘤肿瘤的免疫监视。110只回交小鼠的DNA分型显示Pyv（S）和Mtv-7之间没有重组的证据。在C57 BR/cdJ小鼠中，多瘤病毒特异性CD 8（+）细胞毒性T淋巴细胞对V β 6的强偏倚使用表明，携带这种Mtv-7 SAG反应性V β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Pyv（S）和Mtv-7 sag之间的同一性，并证明了基于内源性超抗原对宿主T细胞库的作用的对病毒诱导的肿瘤的遗传易感性的新机制。
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 V beta domains. DNA typing of 110 backcross mice showed no evidence of recombination between Pyv(S) 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 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.