title: 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.
abstract: 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.
authors.affiliation: Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Peking Union Medical College, Beijing 100005, China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Dai
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Chen
authors.initials: C
authors.lastname: Mo
authors.forename: Lianxian
authors.initials: L
authors.lastname: Cui
authors.forename: Wei
authors.initials: W
authors.lastname: He
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D002051:Burkitt Lymphoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D006367:HeLa Cells; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051718:MutS Homolog 2 Protein / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein