Variable NK cell receptors and their MHC class I ligands in immunity, reproduction and human evolution

Nat Rev Immunol. 2013 Feb;13(2):133-44. doi: 10.1038/nri3370. Epub 2013 Jan 21.


Natural killer (NK) cells have roles in immunity and reproduction that are controlled by variable receptors that recognize MHC class I molecules. The variable NK cell receptors found in humans are specific to simian primates, in which they have progressively co-evolved with MHC class I molecules. The emergence of the MHC-C gene in hominids drove the evolution of a system of NK cell receptors for MHC-C molecules that is most elaborate in chimpanzees. By contrast, the human system of MHC-C receptors seems to have been subject to different selection pressures that have acted in competition on the immunological and reproductive functions of MHC class I molecules. We suggest that this compromise facilitated the development of the bigger brains that enabled archaic and modern humans to migrate out of Africa and populate other continents.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Evolution*
  • Evolution, Molecular
  • Haplotypes
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology*
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Immunity* / genetics
  • Immunity* / immunology
  • Protein Binding
  • Protein Stability
  • Receptors, Natural Killer Cell / genetics
  • Receptors, Natural Killer Cell / immunology*
  • Receptors, Natural Killer Cell / metabolism
  • Reproduction* / genetics
  • Reproduction* / immunology


  • Histocompatibility Antigens Class I
  • Receptors, Natural Killer Cell