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

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.