Molecular structure of the gene products of the human HLA system: isolation and characterization of HLA-A, -B, -C, and Ia antigens

The major histocompatibility region of man (HLA) codes for two groups of polymorphic cell surface membrane antigens. One group comprises the products of the A, B and C loci. The second group represents the Ia (immune-associated) antigens, some of which show a close association with the D locus. The strategy employed for the isolation of these antigens and the establishment of their molecular structures is reviewed. The A, B and C antigens are composed of a 43 000 molecular mass glycosylated polypeptide which carries the polymorphic specificities and which is non-covalently linked to a non-glycosylated polypeptide of molecular mass 12 000, namely β₂-microglobulin. Structural analyses indicate that the A and B antigens have arisen by gene duplication and that the C gene(s) probably arose from the A gene(s). The Ia antigens do not contain β₂-microglobulin but comprise two non-covalently linked glycosylated polypeptides of molecular masses 33 000 and 28 000. Only the 33 000 molecular mass chain is apparently a product of the HLA region.