Abstract
NK cell self-tolerance is maintained by inhibitory receptors specific for MHC class I molecules. Inhibitory NK receptors are also expressed on memory CD8 T cells but their biological relevance on T cells is unclear. In this study, we describe the expression of the Ly49A receptor on a subset of autoreactive T cells which persist in mice double-transgenic for the lymphocytic choriomeningitis virus-derived peptide gp33 and a TCRalphabeta specific for the gp33. No Ly49A-expressing cells are found in TCRalphabeta single-transgenic mice, indicating that the presence of the autoantigen is required for Ly49A induction. Direct evidence for an Ag-specific initiation of Ly49A expression has been obtained in vitro after stimulation of autoreactive TCRalphabeta T cells with the cognate self-Ag. This expression of Ly49A substantially reduces Ag-specific activation of autoreactive T cells. These findings thus suggest that autoantigen-specific induction of inhibitory NK cell receptors on T cells may contribute to peripheral self-tolerance.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Blocking / pharmacology
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Antigens / biosynthesis
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Antigens, Ly / biosynthesis*
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Antigens, Ly / immunology
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Antigens, Ly / physiology
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Antigens, Surface
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Antigens, Viral / genetics
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Antigens, Viral / immunology
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Autoantigens / pharmacology*
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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Glycoproteins / genetics
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Glycoproteins / immunology
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H-2 Antigens / immunology
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H-2 Antigens / metabolism
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Histocompatibility Antigen H-2D
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Immunologic Memory / genetics
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Immunophenotyping
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Killer Cells, Natural / immunology
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Killer Cells, Natural / metabolism
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Lectins, C-Type
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Lymphocytic choriomeningitis virus / immunology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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NK Cell Lectin-Like Receptor Subfamily A
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NK Cell Lectin-Like Receptor Subfamily B
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Peptide Fragments / genetics
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Peptide Fragments / immunology
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Protein Biosynthesis
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Proteins*
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Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Receptors, NK Cell Lectin-Like
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism*
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Viral Proteins / genetics
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Viral Proteins / immunology
Substances
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Antibodies, Blocking
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Antigens
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Antigens, Ly
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Antigens, Surface
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Antigens, Viral
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Autoantigens
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Glycoproteins
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H-2 Antigens
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Histocompatibility Antigen H-2D
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Klra1 protein, mouse
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Lectins, C-Type
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NK Cell Lectin-Like Receptor Subfamily A
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NK Cell Lectin-Like Receptor Subfamily B
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Peptide Fragments
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Proteins
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Receptors, Antigen, T-Cell, alpha-beta
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Receptors, NK Cell Lectin-Like
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Viral Proteins
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glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus