Structural relationships between the DR beta 1 and DR beta 2 subunits in DR4, 7, and w9 haplotypes and the DRw53 (MT3) specificity.
The class II molecules of DR4, DR7, and DRw9 haplotypes were analyzed by immunoprecipitation, followed by two-dimensional gel electrophoresis and N-terminal amino acid sequencing. By using HLA-DR chain-specific monoclonal antibodies, two distinct DR beta-chains were identified. One beta-chain, designated DR beta 2, had a characteristic acidic mobility. In all three DR types the DR beta 2-chains were indistinguishable by two-dimensional gel electrophoresis and partial N-terminal sequencing. A second DR beta-chain designated beta 1 had a more basic mobility on two-dimensional gel electrophoresis, and differed from the DR beta 2-chains by the consistent presence of phenylalanine at position 18. In contrast to the DR beta 2-chains, the DR beta 1-chains were clearly polymorphic, with specific amino acid sequence differences characteristic of each DR type. The monoclonal antibodies 109d6 and 17-3-3S, recognizing distinct polymorphic epitopes similarly correlated with the DRw53 allospecificity, were found to react with different DR beta-chains. The epitope recognized by monoclonal antibody 109d6 was identified on the DR beta 2-chain in the prototypic DR4, DR7, and DRw9 cell lines. However, the DR7, Dw11, DQw3 cell line BEI was unreactive with antibody 109d6 by either immunofluorescence or immunoprecipitation despite the presence of the DRw53 allodeterminant on this cell line. The other DRw53-like monoclonal antibody, 17-3-3S, reacted with the DR beta 1-rather than the DR beta 2-chain in all DR4 and DR7 cell lines tested, including the cell line BEI. However, antibody 17-3-3S did not react with the DRw53-positive DRw9 cell line ISK. These studies suggest that the DRw53 allospecificity is more complex than previously thought and may comprise a number of distinct epitopes encoded by two different DR beta loci.
D000595:Amino Acid Sequence; D000937:Antigen-Antibody Reactions; D002460:Cell Line; D000939:Epitopes / Q000032:analysis / Q000235:genetics / Q000276:immunology; D005838:Genotype; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; D015804:HLA-DR4 Antigen; D015809:HLA-DR7 Antigen; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000235:genetics / Q000276:immunology; D006801:Humans; D013329:Structure-Activity Relationship
D000939:Epitopes; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; D015804:HLA-DR4 Antigen; D015809:HLA-DR7 Antigen; C038988:HLA-DR9 antigen; D000949:Histocompatibility Antigens Class II