KIR expression on self-reactive CD8+ T cells is controlled by T-cell receptor engagement

Nature. 2000 Jan 20;403(6767):325-8. doi: 10.1038/35002105.


Natural killer cell tolerance is maintained by the interaction of killer inhibitory receptors (KIRs) with self-major histocompatibility complex class I gene products. A subset of T cells also expresses inhibitory receptors, but the functional significance of these receptors on T cells is unclear. Here we show that, in the absence of T-cell receptor (TCR) engagement, KIRs expressed on CD8+ T cells are slowly downregulated by KIR ligands expressed on antigen-presenting cells. The resulting expression levels of KIR are no longer able to inhibit T-cell function. In contrast, TCR engagement sustains KIR expression, and re-induces functional levels of KIR expression after ligand-induced downregulation of KIR. Our data indicate that KIR expression on CD8+ T cells in vivo may be maintained through continuous encounters with antigen. As KIR-mediated inhibition of T-cell activation can be bypassed at high antigen concentrations, dynamic KIR expression may mediate T-cell tolerance to self-antigens by sparing self-reactive T cells, thus enabling them to mediate potentially useful immune functions to quantitatively or qualitatively different antigens.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Antigen-Presenting Cells / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Line
  • Cells, Cultured
  • Cytotoxicity, Immunologic
  • Down-Regulation
  • HLA-C Antigens / immunology
  • Humans
  • Interferon-gamma / biosynthesis
  • Ligands
  • Lymphocyte Activation
  • Macrolides*
  • Monophenol Monooxygenase / immunology
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Immunologic / metabolism*
  • Receptors, KIR
  • Self Tolerance


  • Anti-Bacterial Agents
  • HLA-C Antigens
  • HLA-C*70 antigen
  • Ligands
  • Macrolides
  • Receptors, Antigen, T-Cell
  • Receptors, Immunologic
  • Receptors, KIR
  • Interferon-gamma
  • bafilomycin A1
  • Monophenol Monooxygenase