JBC：肿瘤生物标记物hMSH2的识别机制

核蛋白hMSH2是DNA错配修复系统中的重要元件。之前的研究表明，hMSH2很可能是TCRγδ的一种蛋白配体。近日，来自中国医学科学院基础医学研究所的何维教授及其研究组发现：异位表达的人类肿瘤生物标记物hMSH2是一个新发现的内源性配体，可以被人类Vδ2 T细胞识别并引起先天的抗肿瘤抗病毒免疫反应。相关论文发表在3月20日的美国《生化周刊》（Journal of Biological Chemistry）上。

hMSH2在大多数的上皮肿瘤细胞中异位表达，研究人员发现，hMSH2可以与TCRγδ和NKG2D相互作用来促进Vδ2 T细胞介导的肿瘤细胞溶解。此外，在体外，rhMSH2蛋白刺激Vδ2 T细胞的增殖以及IFN-γ的分泌。最后，hMSH2表达被诱导于EBV转化的淋巴样干细胞系的细胞表面，这样的诱导会提高这些LCLs对γδ T细胞介导的细胞溶解的敏感性。

研究数据表明，hMSH2可以作为一个被Vδ2 TCR和NKG2D识别的与肿瘤有关或者是病毒感染有关的抗原，在诱发γδ T细胞对抗肿瘤细胞及病毒感染细胞时起到重要作用。

在肿瘤生成及病毒感染引起的先天的免疫反应中，TCRγδ和NKG2D对异位表达的内源性抗体的识别很有可能会是一个重要的机制。（生物谷Deepblue编译）

doi: 10.1074/jbc.M111.327650
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Ectopically-expressed human tumor biomarker MutS homologue 2 is a novel endogenous ligand that is recognized by human gammadelta T cells to induce innate anti-tumor/virus immunity

Yumei Dai, Hui Chen, Chen Mo, Lianxian Cui and Wei He

Human MutS homologue 2(hMSH2), a nuclear protein, is a critical element of the DNA mismatch repair system. Our previous studies suggest that hMSH2 might be a protein ligand for TCRγδ. Here we show that hMSH2 is ectopically expressed on a large panel of epithelial tumor cells.We found that hMSH2 interacts with both TCRγδ and NKG2D and contributes to Vδ2 T cell mediated cytolysis of tumor cells. Moreover, rhMSH2 protein stimulates the proliferation and IFN-γ secretion of Vδ2 T cells in vitro. Finally, hMSH2 expression is induced on the cell surface of EBV-transformed lymphoblastoid cell lines (LCLs), and the induction increases the sensitivity of these LCLs to γδ T cell-mediated cytolysis.Our data suggest that hMSH2 functions as a tumor-associated or virus infection-related antigen recognized by both Vδ2 TCR and NKG2D, and plays a role in eliciting the immune responses of γδ T cells against tumor and virus-infected cells.The recognition of ectopically surface-expressing endogenous antigen by TCRγδ and NKG2D may be an important mechanism of innate immune response to carcinogenesis and viral infection..