Abstract
The localization of gammadelta T cells within epithelia suggests that these cells may contribute to the down-regulation of epithelial malignancies. We report that mice lacking gammadelta cells are highly susceptible to multiple regimens of cutaneous carcinogenesis. After exposure to carcinogens, skin cells expressed Rae-1 and H60, major histocompatibility complex-related molecules structurally resembling human MICA. Each of these is a ligand for NKG2d, a receptor expressed by cytolytic T cells and natural killer (NK) cells. In vitro, skin-associated NKG2d+ gammadelta cells killed skin carcinoma cells by a mechanism that was sensitive to blocking NKG2d engagement. Thus, local T cells may use evolutionarily conserved proteins to negatively regulate malignancy.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Carcinogens
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Cell Line
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Cytotoxicity, Immunologic
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Dimerization
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Epidermis / immunology*
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Epithelial Cells / immunology
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Histocompatibility Antigens Class I / chemistry
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Histocompatibility Antigens Class I / immunology
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Humans
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Immunologic Surveillance*
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Ligands
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Membrane Proteins / chemistry
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Membrane Proteins / genetics
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Membrane Proteins / immunology*
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Membrane Proteins / metabolism
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Mice
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Mice, Inbred C57BL
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Minor Histocompatibility Antigens / genetics
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Minor Histocompatibility Antigens / immunology
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Minor Histocompatibility Antigens / metabolism
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Molecular Sequence Data
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NK Cell Lectin-Like Receptor Subfamily K
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Protein Conformation
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Protein Folding
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Receptors, Antigen, T-Cell, alpha-beta / immunology
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Receptors, Antigen, T-Cell, gamma-delta / immunology*
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Receptors, Immunologic / immunology*
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Receptors, Immunologic / metabolism
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Receptors, Natural Killer Cell
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Recombinant Fusion Proteins / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Skin Neoplasms / chemically induced
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Skin Neoplasms / immunology*
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T-Lymphocyte Subsets / immunology*
Substances
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Carcinogens
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Histocompatibility Antigens Class I
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KLRK1 protein, human
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Klrk1 protein, mouse
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Ligands
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MHC class I-related chain A
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Membrane Proteins
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Minor Histocompatibility Antigens
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NK Cell Lectin-Like Receptor Subfamily K
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Raet1a protein, mouse
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Receptors, Antigen, T-Cell, alpha-beta
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Receptors, Antigen, T-Cell, gamma-delta
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Receptors, Immunologic
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Receptors, Natural Killer Cell
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Recombinant Fusion Proteins
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minor H antigen H60