Molecular analysis of the genes for human class II antigens of the major histocompatibility complex

Different cDNA clones have been isolated that encode each of the three chains of HLA-DR antigens: α, intermediate and β, as well as another β chain, most likely DC. Whereas the DR α and intermediate chains seem encoded by single genes, the DR and DC β chains are most likely encoded by multiple genes; furthermore, their polymorphism can be readily detected by restriction analysis of cellular DNA. Several genomic DNA clones were isolated for the DR and DC β chain genes and for the intermediate chain gene. The sum of all distinct cDNA clones and genomic DNA clones for HLA-DR β chains, isolated from a heterozygous cell line, represent five genes. This implies the existence of at least three nonallelic DR β chain genes in addition to the DC β chain genes. The complete sequence of one of the DR β chains is presented. A genomic DNA clone for a DR β chain was transferred into mouse L cells and found to be expressed into RNA of the same size as DR β mRNA. The finding, among the genes for class II antigens, of multiple genes for the β chain of HLA-DR, distinct from those of other known subregions such as DC, emphasizes the importance of gene transfer experiments, where individual genes can be expressed and tested for their functional role in the immune response.