Functions of nonclassical MHC and non-MHC-encoded class I molecules

Curr Opin Immunol. 1999 Feb;11(1):100-8. doi: 10.1016/s0952-7915(99)80018-1.


Fascinating recent discoveries have focused attention on the nonclassical class I molecules. They can exert their function at most levels of the immune response, being part of both innate and adaptive immune systems. They not only have specialized antigen-presentation functions but also play important immunoregulatory roles: HLA-E regulates natural killer cells by interacting with CD94/NKG2 receptors; the MIC (MHC class I chain related) glycoproteins appear crucial to the activation of gammadelta T cells in the gastrointestinal epithelium; HLA-G may play a role in controlling the immune response to the fetus; and CD1 molecules are important in defense against bacterial infections, as well as in the development and regulation of a subset of NKT cells expressing a highly restricted TCR repertoire; however not all nonclassical class I molecules have an immunological function, as demonstrated by HFE which is implicated in iron metabolism.

Publication types

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

MeSH terms

  • Animals
  • Antigens, CD1 / physiology
  • HLA Antigens / physiology
  • HLA-G Antigens
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I / physiology*
  • Humans
  • Immunity
  • Membrane Proteins*


  • Antigens, CD1
  • HFE protein, human
  • HLA Antigens
  • HLA-E antigen
  • HLA-G Antigens
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I
  • MHC class I-related chain A
  • MICB antigen
  • Membrane Proteins
  • Q surface antigens