Allelic polymorphism and complexity of the genes for HLA-DR β-chains—direct analysis by DNA–DNA hybridization

HLA-DR antigens are highly polymorphic cell surface glyco-proteins involved in the control of the immune response. They are important in allograft rejection and in their linkage to certain disease susceptibilities. The allelic polymorphism of HLA-DR antigens is carried by the β-chain. We have isolated cDNA clones encoding several distinct HLA-DR β chains and other β-chains from related loci, including DC, making it possible to analyse this complex genetic system directly by Southern hybridization and to demonstrate the polymorphism of these DNA sequences in the human genome. Hybridization patterns obtained with DNA of one DR-heterozygous and three DR-homozygous cell lines suggest the presence of a number of different genes for these two β-chain loci. Extensive polymorphism of the restriction pattern was detected in individuals of different DR specificities, with each of the three restriction enzymes used. Analysis of HLA-DR directly at the DNA level may lead to a simpler typing procedure and may eventually refine the specificities so far determined either serologically or by cellular assay.