MIC and other NKG2D ligands: from none to too many

Curr Opin Immunol. 2005 Oct;17(5):505-9. doi: 10.1016/j.coi.2005.07.016.


NKG2D, a prime activatory receptor on human NK, CD8(+) alphabeta and gammadelta cells, has a variety of ligands, which, despite sharing membership of the MHC class I structural club, display an array of unique features. Chronologically, human MIC molecules were the first NKG2D ligands to be identified. Then came RAET1 (ULBP) molecules, which were identified in both man and mouse, as well as H60 and MULT1, which have no counterparts in man to date. The question remains as to why, more than how, the evolutionary conserved, apparently monomorphic, single copy, NKG2D, can/should adapt to this variety of ligands, and when it does, what is the evolutionary advantage of this profusion of ligands for a single receptor?

Publication types

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

MeSH terms

  • Animals
  • Genes, MHC Class I / physiology*
  • Humans
  • Ligands
  • NK Cell Lectin-Like Receptor Subfamily K
  • Polymorphism, Genetic
  • Receptors, Immunologic / genetics*
  • Receptors, Immunologic / immunology*
  • Receptors, Natural Killer Cell


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