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

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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 [WALK, ER, NIN, HA, PRIESS, FS, EM, THO, LS40, BIN40, KT3, HAS-15, JHa, SST, KT2, KT13, TAS]. 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.