Protection from autoimmune disease as the third function of the major histocompatibility gene complex

Lancet. 1987 Aug 1;2(8553):245-9. doi: 10.1016/s0140-6736(87)90830-0.

Abstract

The collection of genes known as the major histocompatibility gene complex (MHC) appears to subserve three functions. Firstly, its class I genes, coding for antigens on all nucleated cells, assist clones of cytotoxic T cells to kill virus-infected cells quickly, without being muffled by the myriad numbers of free virus particles. Secondly, the absence of autoimmunity to both class I and class II MHC antigens shows that they impose unbreakable tolerances on the immune repertoire. The class II antigens, which are confined to B lymphocytes (if their apparent occurrence on other dividing cells is a cross-reaction), may have the sole function of tolerance induction, supplementing this activity of the class I antigens. Both sets of MHC antigens serve to diversify immunity-repertoire gaps among individuals of a population, thus hampering epidemic spread of infection and providing a diversity of immunoreactivity that favours survival of at least some members of a population in the face of pestilence. Thirdly, the permanence of the MHC tolerance inductions affords a powerful, adaptable mechanism for curtailment of reproductively disadvantageous autoimmune disease liable to arise through somatic mutations in lymphocytes multiplying under drive from a microbial antigenic stimulus.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / prevention & control*
  • HLA Antigens / genetics
  • Histocompatibility Antigens / genetics
  • Humans
  • Immune Tolerance
  • Major Histocompatibility Complex*
  • Mice

Substances

  • HLA Antigens
  • Histocompatibility Antigens