Young J A, Wilkinson D, Bodmer W F, Trowsdale J
Proc Natl Acad Sci U S A. 1987 Jul;84(14):4929-33. doi: 10.1073/pnas.84.14.4929.
cDNA clones representing products of the DR7 and DRw53 beta-chain genes were isolated from the human B-lymphoblastoid cell line MANN (DR7,DRw53,DQw2, DPw2). The DRw53 beta sequence was identical to a DRw53 beta sequence derived from cells with a DR4 haplotype. In contrast, the DR7 beta sequence was as unrelated to DR4 beta sequence as it was to other DR beta-related genes, except at the 3'-untranslated region. These results suggest that the DR7 and DR4 haplotypes may have been derived relatively recently from a common ancestral haplotype and that the DR4 and DR7 beta-chain genes have undergone more rapid diversification in their beta 1 domains, most probably as a result of natural selection, than have the DRw53 beta-chain genes. Short tracts of sequence within the DR7 and DRw53 beta 1 domains were shared with other DR beta sequences, indicating that exchanges of genetic information between beta 1 domains of DR beta-related genes have played a part in their evolution. Serological analysis of mouse L-cell transfectants expressing surface HLA-DR7 molecules, confirmed by antibody binding and allelic sequence comparisons, identified amino acid residues that may be critical to the binding of a monomorphic DR- and DP-specific monoclonal antibody.
从人B淋巴母细胞系MANN(DR7、DRw53、DQw2、DPw2)中分离出代表DR7和DRw53β链基因产物的cDNA克隆。DRw53β序列与来自具有DR4单倍型细胞的DRw53β序列相同。相比之下,DR7β序列与DR4β序列的关系,与其与其他DRβ相关基因的关系一样不相关,除了在3'非翻译区。这些结果表明,DR7和DR4单倍型可能是相对较近地从一个共同的祖先单倍型衍生而来,并且DR4和DR7β链基因在其β1结构域中经历了比DRw53β链基因更快的多样化,最有可能是自然选择的结果。DR7和DRw53β1结构域内的短序列片段与其他DRβ序列共享,表明DRβ相关基因的β1结构域之间的遗传信息交换在它们的进化中发挥了作用。通过抗体结合和等位基因序列比较证实,对表达表面HLA - DR7分子的小鼠L细胞转染体进行血清学分析,确定了可能对单态DR和DP特异性单克隆抗体结合至关重要的氨基酸残基。