Hildebrand W H, Domena J D, Shen S Y, Lau M, Terasaki P I, Bunce M, Marsh S G, Guttridge M G, Bias W B, Parham P
Department of Cell Biology and Microbiology, Stanford University, California.
Tissue Antigens. 1994 Apr;43(4):209-18. doi: 10.1111/j.1399-0039.1994.tb02327.x.
HLA-B15 embraces a multiplicity of antigenic specificities which vary in their distribution amongst human populations. To correlate B15 molecular structure with the serological picture we have sequenced alleles encoding the various subspecificities of the B15 antigen: B62, B63, B75, B76 and B77, and a number of "variants" of these antigens including the 8w66 split of B63. HLA-B63 (B1517) and 8w66 (B1516) heavy chains have sequence identity to B17 in the alpha 1 helix correlating with the antigenic crossreactivity of these molecules. HLA-B77(B1513) and B75 (B1502) heavy chains differ solely in segments determining the Bw4 and Bw6 public epitopes, consistent with the serological description of the B77 and B75 antigens. One allele encoding the B76 antigen (B1512) appears to be the product of gene conversion between the HLA-A and -B loci and differs from B1501 in codons 166 and 167. In contrast, a second allele encoding the B76 antigen (B1514) differs from B1501 by an unrelated substitution in codon 167 which confers similarily with B45, an antigen crossreactive with B76. A third allele encoding B76, B1519, differs from B1512 by a unique point substitution in exon 4. Three alleles encoding variant B15 and B62 antigens (B1508, B1511 and B1515) differ from B1501 by localized clusters of substitutions that probably result from interallelic conversion. The B15 sequences described in this paper, in combination with those previously determined, define a family of 22 alleles, including those encoding the B46 and B70 antigens. Within this family the patterns of allelic substitution are analogous to those of other HLA-A and -B families, in that pairwise differences almost always involve functional positions of the antigen recognition site and recombination is the major agent of diversification.
HLA - B15包含多种抗原特异性，这些特异性在人群中的分布有所不同。为了将B15的分子结构与血清学特征相关联，我们对编码B15抗原各种亚特异性（B62、B63、B75、B76和B77）以及这些抗原的一些“变体”（包括B63的8w66裂解产物）的等位基因进行了测序。HLA - B63（B1517）和8w66（B1516）重链在α1螺旋中与B17具有序列同一性，这与这些分子的抗原交叉反应性相关。HLA - B77（B1513）和B75（B1502）重链仅在决定Bw4和Bw6公共表位的片段上有所不同，这与B77和B75抗原的血清学描述一致。一个编码B76抗原的等位基因（B1512）似乎是HLA - A和 - B基因座之间基因转换的产物，在密码子166和167处与B1501不同。相比之下，另一个编码B76抗原的等位基因（B1514）在密码子167处与B1501存在一个不相关的替换，这使其与B45具有相似性，B45是一种与B76交叉反应的抗原。第三个编码B76的等位基因B1519，在外显子4中与B1512存在一个独特的点替换。三个编码变体B15和B62抗原的等位基因（B1508、B1511和B1515）与B1501的差异在于局部成簇的替换，这可能是等位基因间转换的结果。本文描述的B15序列与先前确定的序列相结合，定义了一个包含22个等位基因的家族，包括那些编码B46和B70抗原的等位基因。在这个家族中，等位基因替换模式与其他HLA - A和 - B家族类似，即成对差异几乎总是涉及抗原识别位点的功能位置，并且重组是多样化的主要因素。
