Immunology
Ectopically Expressed Human Tumor Biomarker MutS Homologue 2 Is a Novel Endogenous Ligand That Is Recognized by Human γδ T Cells to Induce Innate Anti-tumor/Virus Immunity*

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Human (h) MutS homologue 2, 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, recombinant human MSH2 protein stimulates the proliferation and IFN-γ secretion of Vδ2 T cells in vitro. Finally, hMSH2 expression is induced on the cell surface of Epstein-Barr virus-transformed lymphoblastoid cell lines, and the induction increases the sensitivity of these lymphoblastoid cell lines 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 it plays a role in eliciting the immune responses of γδ T cells against tumor- and virus-infected cells. The recognition of ectopic surface-expressing endogenous antigen by TCRγδ and NKG2D may be an important mechanism of innate immune response to carcinogenesis and viral infection.

Antigen
Innate Immunity
Natural Killer (NK) Cell
T Cell Receptor
Tumor Marker
gamma delta T Cells
Anti-tumor Immunity
Anti-virus Immunity
Endogenous Ligand
Human MutS Homologue 2 (MSH2)

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This work was supported by Grant 30930083 from the National Natural Science Foundation.