核蛋白hMSH2是DNA錯配修復(fù)系統(tǒng)中的重要元件。之前的研究表明,，hMSH2很可能是TCRγδ的一種蛋白配體。近日,，來自中國醫(yī)學(xué)科學(xué)院基礎(chǔ)醫(yī)學(xué)研究所的何維教授及其研究組發(fā)現(xiàn)：異位表達(dá)的人類腫瘤生物標(biāo)記物hMSH2是一個新發(fā)現(xiàn)的內(nèi)源性配體,，可以被人類Vδ2 T細(xì)胞識別并引起先天的抗腫瘤抗病毒免疫反應(yīng),。相關(guān)論文發(fā)表在3月20日的美國《生化周刊》（Journal of Biological Chemistry）上。
hMSH2在大多數(shù)的上皮腫瘤細(xì)胞中異位表達(dá),，研究人員發(fā)現(xiàn)，hMSH2可以與TCRγδ和NKG2D相互作用來促進(jìn)Vδ2 T細(xì)胞介導(dǎo)的腫瘤細(xì)胞溶解,。此外,，在體外,，rhMSH2蛋白刺激Vδ2 T細(xì)胞的增殖以及IFN-γ的分泌,。最后，hMSH2表達(dá)被誘導(dǎo)于EBV轉(zhuǎn)化的淋巴樣干細(xì)胞系的細(xì)胞表面,，這樣的誘導(dǎo)會提高這些LCLs對γδ T細(xì)胞介導(dǎo)的細(xì)胞溶解的敏感性。
研究數(shù)據(jù)表明,，hMSH2可以作為一個被Vδ2 TCR和NKG2D識別的與腫瘤有關(guān)或者是病毒感染有關(guān)的抗原，在誘發(fā)γδ T細(xì)胞對抗腫瘤細(xì)胞及病毒感染細(xì)胞時起到重要作用,。
在腫瘤生成及病毒感染引起的先天的免疫反應(yīng)中，TCRγδ和NKG2D對異位表達(dá)的內(nèi)源性抗體的識別很有可能會是一個重要的機(jī)制,。（生物谷Deepblue編譯）
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..
