Peptide antagonism as a mechanism for NK cell activation

Proc Natl Acad Sci U S A. 2010 Jun 1;107(22):10160-5. doi: 10.1073/pnas.0913745107. Epub 2010 May 3.

Abstract

Inhibition of natural killer (NK) cells is mediated by MHC class I receptors including the killer cell Ig-like receptor (KIR). We demonstrate that HLA-C binding peptides can function as altered peptide ligands for KIR and antagonize the inhibition mediated by KIR2DL2/KIR2DL3. Antagonistic peptides promote clustering of KIR at the interface of effector and target cells, but do not result in inhibition of NK cells. Our data show that, as for T cells, small changes in the peptide content of MHC class I can regulate NK cell activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Line
  • HLA-C Antigens / metabolism
  • Humans
  • Killer Cells, Natural / immunology*
  • Kinetics
  • Ligands
  • Lymphocyte Activation
  • Oligopeptides / genetics
  • Oligopeptides / immunology
  • Oligopeptides / metabolism
  • Phosphorylation
  • Protein Binding
  • Proto-Oncogene Proteins c-vav / metabolism
  • Receptors, KIR / antagonists & inhibitors
  • Receptors, KIR / immunology
  • Receptors, KIR2DL2 / antagonists & inhibitors
  • Receptors, KIR2DL2 / metabolism
  • Receptors, KIR2DL3 / antagonists & inhibitors
  • Receptors, KIR2DL3 / metabolism
  • Signal Transduction

Substances

  • HLA-C Antigens
  • KIR2DL2 protein, human
  • KIR2DL3 protein, human
  • Ligands
  • Oligopeptides
  • Proto-Oncogene Proteins c-vav
  • Receptors, KIR
  • Receptors, KIR2DL2
  • Receptors, KIR2DL3
  • VAV1 protein, human