Two opposite signaling outputs are driven by the KIR2DL1 receptor in human CD4+ T cells

Blood. 2008 Sep 15;112(6):2381-9. doi: 10.1182/blood-2007-12-127779. Epub 2008 Jun 23.


Inhibitory killer Ig-like receptors (KIR), expressed by human natural killer cells and effector memory CD8(+) T-cell subsets, bind HLA-C molecules and suppress cell activation through recruitment of the Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1). To further analyze the still largely unclear role of inhibitory KIR receptors on CD4(+) T cells, KIR2DL1 transfectants were obtained from a CD4(+) T-cell line and primary cells. Transfection of CD4(+) T cells with KIR2DL1 dramatically increased the T-cell receptor (TCR)-induced production of interleukin-2 independently of ligand binding but inhibited TCR-induced activation after ligation. KIR-mediated costimulation of TCR activation involves intact KIR2DL1-ITIM phosphorylation, SHP-2 recruitment, and PKC- phosphorylation. Synapses leading to activation were characterized by an increase in the recruitment of p-Tyr, SHP-2, and p-PKC-, but not of SHP-1. Interaction of KIR2DL1 with its ligand led to a strong synaptic accumulation of KIR2DL1 and the recruitment of SHP-1/2, inhibiting TCR-induced interleukin-2 production. KIR2DL1 may induce 2 opposite signaling outputs in CD4(+) T cells, depending on whether the KIR receptor is bound to its ligand. These data highlight unexpected aspects of the regulation of T cells by KIR2DL1 receptors, the therapeutic manipulation of which is currently being evaluated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Humans
  • Interleukin-2 / biosynthesis
  • Isoenzymes / metabolism
  • Protein Kinase C / metabolism
  • Protein Kinase C-theta
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6 / metabolism
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, KIR2DL1 / genetics
  • Receptors, KIR2DL1 / metabolism*
  • Signal Transduction / immunology*
  • Transfection


  • Interleukin-2
  • Isoenzymes
  • Receptors, Antigen, T-Cell
  • Receptors, KIR2DL1
  • PRKCQ protein, human
  • Protein Kinase C
  • Protein Kinase C-theta
  • PTPN11 protein, human
  • PTPN6 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6