Differential effect of polymorphism at HLA-DR1 beta-chain positions 85 and 86 on binding and recognition of DR1-restricted antigenic peptides.
The valine-glycine dimorphism at position 86 of the DR beta-chain exhibited by most DR alleles has been shown to affect peptide binding. We demonstrate that DR1-restricted antigenic peptides differ in the extent to which binding is affected by amino acid substitution at positions 85 and 86 of the DR1 beta-chain. Binding of peptides derived from influenza hemagglutinin (HA306-320) and tetanus toxin (TT830-843) but not influenza matrix protein (MP19-31) was diminished on cells expressing DR1 beta-chains encoded by DRB1*0102 relative to DRB1*0101. The presence of tyrosine within HA306-320 and TT830-843 vs leucine within MP19-31 at a single DR contact position was revealed by alignment of the peptides according to a DR-binding motif. HA306-320 bearing leucine at this position (HA 306-320L309) bound to DR1 possessing either DRB1*0101- or DRB1*0102-encoded beta-chains suggesting that DR residues may discriminate among peptides based upon amino acid identity at a single position within the peptide. Furthermore, whereas all HA306-320-specific T cell clones recognized HA306-320L309 in the context of DR1 molecules possessing DRB1*0102-encoded beta-chains, some T cell clones failed to recognize HA306-320L309 in the context of DR1 molecules possessing DRB1*0101-encoded beta-chains. These results suggest that peptide conformation may also be affected by amino acid substitution at positions 85 and or 86 of the DR1 beta-chain.
Newton-Nash
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Immunogenetics Research, Blood Research Institute, Milwaukee, Wisconsin 53233.
Eckels
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D000483:Alleles; D000595:Amino Acid Sequence; D001667:Binding, Competitive; D000939:Epitopes / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D011110:Polymorphism, Genetic; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology
D000939:Epitopes; D006684:HLA-DR Antigens; D010446:Peptide Fragments