The HLA System

Abstract

The pioneer studies by J. Dausset, using leukocyte agglutinins from multiple transfused patients, and J. J. van Rood and R. Payne, using serum from women immunized by leukocytes during pregnancy, were followed by intensive studies which succeeded in defining a series of highly polymorphic loci very closely linked with each other on the short arm of chromosome 6. These studies received a great impetus from the experimental work in mice which had previously demonstrated homologous closely linked loci determining antigens which Gorer and Snell showed were important histocompatibility antigens, determining the rejection or survival of transplanted tissues (the H-2 system). The subsequent findings (1) that under experimental conditions humoral and cellular immune responses to certain synthetic antigens were determined by genes in the H-2 regions, and (2) that the occurrence of virus induced leukaemia was influenced by genes in this region, provided important clues as to the likely biological roles of this chromosomal region in immune regulation and in determining susceptibility or resistance to disease. For the clinical geneticist concerned with the analysis of the complex genetics of more or less common disorders, the findings of the associations between certain of the HLA antigens and many of these diseases have provided an important tool for genetic research. This has acted as a stimulus for new ideas concerning the pathogenesis of many clinical conditions. For a general review see Bodmer^l.