Linkage Map of Three HLA-DR β -Chain Genes: Evidence for a Recent Duplication Event

The predominant class II, or Ia, antigen of the human major histocompatibility complex is HLA-DR. It consists of an α and a β chain, the latter being responsible for the remarkable polymorphism of these Ia antigens. Studies with cloned genes had shown the existence of more than one DR β -chain locus. We have isolated about 100 kilobases of the HLA-DR β -chain gene region from a cosmid library generated from a consanguineous homozygous B-cell line of the DR3 haplotype. Three HLA-DR β -chain genes have been characterized. They are arranged in a head-to-tail orientation. One of the genes lacks the region encoding the first domain of the DR β chain. The two other genes are transcribed, as shown by RNA blot hybridization analysis. A striking restriction site homology has been found within the DR β -chain gene cluster, suggesting a recent duplication event involving at least 25 kilobases of DNA. Moreover, the molecular map of DR β chain genes cloned from B-cell lines of two other HLA-DR haplotypes shows extensive homology between alleles of a given DR β -chain locus.