HLA factors and immune function

Abstract

The HLA system is the major histocompatibility system (MHS) in man and contains a variety of closely linked genes, which control a large number of alloantigens, some complement components, and certain immune responses. The alloantigens are of three different kinds: (i) so-called "classical" or serologically detectable (SD) antigens which are present on all nucleated cells and controlled by genes of at least three different loci; (ii) MLC (= mixed lymphocyte culture = LD = lymphocyte dependent) antigens which are as yet only recognizable by in vitro culture assays; (iii) Ia (= immune-associated) antigens which (like MLC antigens) primarily are present on B lymphocytes and which can be detected serologically. Our knowledge of immune-response (Ir) determinants in man is as yet rather limited but by inference from studies of MHS in mice, guinea-pigs, and rhesus monkeys it is almost certain that HLA contains such genes. Immune response genes control in a dominant way the ability to respond specifically with IgG antibody production and cell-mediated immunity to certain specific antigens. Ir genes are closely linked to the MLC and Ia genes. They seem to be particularly important for immune responses involving T lymphocyte function (including T-B cell cooperation), and it seems likely that they code for "antibody-like", carrier-specific immune receptors on T cells. Evidence that HLA contains Ir determinants derives from the observations (i) that a variety of "immunopathic" disorders are associated with HLA factors; (ii) that ragweed hayfever seems to be inherited with certain HLA types within families; and (iii) that the occurrence of anti-adrenal antibodies is associated with HLA in Addison's disease. Autoimmune thyreoiditis is controlled by the MHS in mice and chickens, and in analogy, Graves' disease is associated with HLA in man.