Genetic and Biological Aspects of the HL-A System of Human Histocompatibility

The HL-A system of leukocyte group antigens is a system of great complexity and polymorphism, governed by an autosomal region which includes a number of subunits or subloci. It constitutes the principal system of histo-compatibility in man.

Extensive population and family studies have resulted in the identification of two HL-A subloci. The first sublocus determines antigens HL-A 1, 2, 3, 9, Da 15 and Da 17 as alternative alleles. Antigens HL-A 5, 7, 8, Da 4, Da 6, HN, and probably Da 9 and Da 18 are determined in similar fashion at a second sublocus. The products of 20 per cent of the genes of the first sublocus, and of 29 per cent of the genes of the second sublocus are still unknown.

Study of 113 families has documented 226 human HL-A genotypes and 452 haplotypes. The observed gene and haplotype frequencies were in close agreement with the anticipated values calculated on the basis of Mendelian laws. This result supports the concept that the HL-A system is in equilibrium.

Although the HL-A system plays a major role as a determinant of human allograft responses, its primordial function may be of relevance to other fundamental biological problems, with particular reference to host defenses against microorganisms, viruses and neoplastic cells.