Electrophoretic analysis of human HLA-DR antigens from HLA-DR4 homozygous cell lines: correlation between beta-chain diversity and HLA-D.

Abstract

Two-dimensional gel electrophoresis of immunoprecipitated human HLA-DR antigens from cells expressing the HLA-DR4 haplotype shows distinct clustering of beta-chain patterns. Six unique electrophoretic variants were observed among 17 HLA-DR4 homozygous cell lines (HCL) analyzed. These patterns correlate precisely with the HLA-D phenotype of the HCL donor as determined by reactivity in mixed lymphocyte culture. All DR4 HCL that belong to one of the well-defined HLA-D antigen groups (Dw4, Dw10, LD "40", LD "DYT", LD "KT2", or LD "TAS") have identical DR beta-chain patterns; DR4 HCL belonging to different HLA-D antigen groups do not. The concordance of the functional expression in mixed lymphocyte culture of a specific D phenotype with a distinct DR beta-chain pattern on gel analysis provides a direct structural basis for understanding the genetic control of HLA-D polymorphisms; HLA-D specificities as revealed by T-cell recognition in mixed lymphocyte culture thus might be accounted for by DR beta-chain polymorphisms. The extent of this beta-chain diversity within a single DR haplotype may aid in understanding variations in Ia-regulated functions, such as Ir gene control and certain disease susceptibilities.