Cutting edge: stimulation with the cognate self-antigen induces expression of the Ly49A receptor on self-reactive T cells which modulates their responsiveness.
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.
Saurer
Leslie
L
Institute of Pathology, Division of Immunopathology, University of Bern, Bern, Switzerland.
Seibold
Inge
I
Vallan
Claudio
C
Held
Werner
W
Mueller
Christoph
C
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000941:Antigens / Q000096:biosynthesis; D000950:Antigens, Ly / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology; D000954:Antigens, Surface; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D001324:Autoantigens / Q000494:pharmacology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism; D064532:Histocompatibility Antigen H-2D; D007156:Immunologic Memory / Q000235:genetics; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055650:NK Cell Lectin-Like Receptor Subfamily A; D055651:NK Cell Lectin-Like Receptor Subfamily B; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D014176:Protein Biosynthesis; D011506:Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics; D055630:Receptors, NK Cell Lectin-Like; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
D019138:Antibodies, Blocking; D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D000956:Antigens, Viral; D001324:Autoantigens; D006023:Glycoproteins; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; C527088:Klra1 protein, mouse; D037181:Lectins, C-Type; D055650:NK Cell Lectin-Like Receptor Subfamily A; D055651:NK Cell Lectin-Like Receptor Subfamily B; D010446:Peptide Fragments; D011506:Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D055630:Receptors, NK Cell Lectin-Like; D014764:Viral Proteins; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus