Klohe E, Fu X T, Ballas M, Karr R W
Department of Veterans Affairs Medical Center, Iowa City, Iowa.
Hum Immunol. 1993 May;37(1):51-8. doi: 10.1016/0198-8859(93)90142-n.
The purpose of this study was to identify polymorphic residues in HLA-DR beta chains that are involved in the epitopes recognized by DRw52-like mAbs. Flow cytometric analysis of antibody binding to mouse fibroblast transfectants expressing wild-type or mutant DRw52-associated DR beta chains demonstrated that the amino acid at position 77, which is predicted to be on a solvent-accessible surface of the alpha-helix, contributes to the epitopes recognized by the 7.3.19.1 and 21r5 mAbs. In contrast, residues that are not predicted to occupy accessible positions on the alpha-helix contribute to binding of the I-LR2 and UL-52 mAbs. Substitutions at positions 10, 12, and 51, but not 9, 11, and 13, affect these epitopes. It is interesting that antibody binding is influenced by amino acid substitutions at DR beta positions 10 and 12 because the class II model predicts that residues at these positions are located in the middle of the floor of the peptide-binding site, with their side chains pointing down. These findings emphasize the functional importance of polymorphic residues whose side chains are not predicted to point into or up from the antigen-binding site and they raise the possibility that peptides contribute to the generation of these epitopes.
本研究的目的是鉴定HLA - DRβ链中与DRw52样单克隆抗体识别的表位相关的多态性残基。对表达野生型或突变型DRw52相关DRβ链的小鼠成纤维细胞转染体进行抗体结合的流式细胞术分析表明，预计位于α螺旋溶剂可及表面的第77位氨基酸，对7.3.19.1和21r5单克隆抗体识别的表位有贡献。相反，预计不在α螺旋可及位置的残基，对I - LR2和UL - 52单克隆抗体的结合有贡献。第10、12和51位的取代，但不是第9、11和13位的取代，会影响这些表位。有趣的是，抗体结合受DRβ链第10和12位氨基酸取代的影响，因为II类模型预测这些位置的残基位于肽结合位点底部中间，其侧链向下。这些发现强调了多态性残基的功能重要性，其侧链预计不会指向抗原结合位点或从抗原结合位点向上，并且它们增加了肽有助于这些表位产生的可能性。
