Cutting edge: stimulation with the cognate self-antigen induces expression of the Ly49A receptor on self-reactive T cells which modulates their responsiveness

J Immunol. 2003 Dec 15;171(12):6334-8. doi: 10.4049/jimmunol.171.12.6334.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Blocking / pharmacology
  • Antigens / biosynthesis
  • Antigens, Ly / biosynthesis*
  • Antigens, Ly / immunology
  • Antigens, Ly / physiology
  • Antigens, Surface
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology
  • Autoantigens / pharmacology*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Glycoproteins / genetics
  • Glycoproteins / immunology
  • H-2 Antigens / immunology
  • H-2 Antigens / metabolism
  • Histocompatibility Antigen H-2D
  • Immunologic Memory / genetics
  • Immunophenotyping
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Lectins, C-Type
  • Lymphocytic choriomeningitis virus / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • NK Cell Lectin-Like Receptor Subfamily A
  • NK Cell Lectin-Like Receptor Subfamily B
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology
  • Protein Biosynthesis
  • Proteins*
  • Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, NK Cell Lectin-Like
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*
  • Viral Proteins / genetics
  • Viral Proteins / immunology

Substances

  • Antibodies, Blocking
  • Antigens
  • Antigens, Ly
  • Antigens, Surface
  • Antigens, Viral
  • Autoantigens
  • Glycoproteins
  • H-2 Antigens
  • Histocompatibility Antigen H-2D
  • Klra1 protein, mouse
  • Lectins, C-Type
  • NK Cell Lectin-Like Receptor Subfamily A
  • NK Cell Lectin-Like Receptor Subfamily B
  • Peptide Fragments
  • Proteins
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, NK Cell Lectin-Like
  • Viral Proteins
  • glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus