Promiscuity and the single receptor: NKG2D

Nat Rev Immunol. 2007 Sep;7(9):737-44. doi: 10.1038/nri2144. Epub 2007 Aug 3.


NKG2D (natural-killer group 2, member D) is a powerful activating receptor expressed by natural killer (NK) cells and T cells that regulates immune responses during infection, cancer and autoimmunity. NKG2D ligands comprise a diverse array of MHC-class-I-related proteins that are upregulated by cellular stress. Why is it beneficial for the host to have so many ligands for the same receptor? In this Opinion article, we propose that although competition with viruses is the most likely evolutionary drive for this diversity, there might be other explanations.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Killer Cells, Natural / immunology*
  • Ligands
  • Mice
  • NK Cell Lectin-Like Receptor Subfamily K
  • Neoplasms / immunology
  • Receptors, Immunologic / metabolism*
  • Receptors, Natural Killer Cell
  • T-Lymphocytes / immunology*


  • Histocompatibility Antigens Class I
  • KLRK1 protein, human
  • Klrk1 protein, mouse
  • Ligands
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell