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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Biomarkers, Tumor / biosynthesis
-
Biomarkers, Tumor / genetics
-
Biomarkers, Tumor / immunology*
-
Burkitt Lymphoma / genetics
-
Burkitt Lymphoma / immunology
-
Burkitt Lymphoma / metabolism*
-
Cell Line, Transformed
-
Cell Proliferation
-
HeLa Cells
-
Herpesvirus 4, Human / genetics
-
Herpesvirus 4, Human / immunology*
-
Herpesvirus 4, Human / metabolism
-
Humans
-
Immunity, Innate*
-
Interferon-gamma / genetics
-
Interferon-gamma / immunology
-
Interferon-gamma / metabolism
-
MutS Homolog 2 Protein / biosynthesis
-
MutS Homolog 2 Protein / genetics
-
MutS Homolog 2 Protein / immunology*
-
NK Cell Lectin-Like Receptor Subfamily K / biosynthesis
-
NK Cell Lectin-Like Receptor Subfamily K / genetics
-
NK Cell Lectin-Like Receptor Subfamily K / immunology
-
Neoplasms, Glandular and Epithelial / genetics
-
Neoplasms, Glandular and Epithelial / immunology*
-
Neoplasms, Glandular and Epithelial / metabolism
-
Neoplasms, Glandular and Epithelial / pathology
-
Receptors, Antigen, T-Cell, gamma-delta / biosynthesis
-
Receptors, Antigen, T-Cell, gamma-delta / genetics
-
Receptors, Antigen, T-Cell, gamma-delta / immunology*
-
T-Lymphocytes / immunology*
-
T-Lymphocytes / metabolism
Substances
-
Biomarkers, Tumor
-
KLRK1 protein, human
-
NK Cell Lectin-Like Receptor Subfamily K
-
Receptors, Antigen, T-Cell, gamma-delta
-
Interferon-gamma
-
MSH2 protein, human
-
MutS Homolog 2 Protein