HLA-B15 - A WIDESPREAD AND DIVERSE FAMILY OF HLA-B ALLELES
HLA-B15 - A WIDESPREAD AND DIVERSE FAMILY OF HLA-B ALLELES
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DOI：
10.1111/j.1399-0039.1994.tb02327.x
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发表时间：
1994-04-01
期刊：
影响因子：
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通讯作者：
PARHAM, P
中科院分区：
文献类型：
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作者：
HILDEBRAND, WH;DOMENA, JD;PARHAM, P
HLA-B15包含多种抗原特异性，其在人群中的分布不同。为了将B15分子结构与血清学图像相关联，我们对编码B15抗原的各种亚特异性的等位基因进行了测序：B62、B63、B75、B76和B77，以及这些抗原的许多“变体"，包括B63的8 w 66分裂。HLA-B63（B*1517）和8 w 66（B*1516）重链在α 1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（B*1513）和B75（B*1502）重链的区别仅在于决定Bw 4和Bw 6公共表位的区段，这与B77和B75抗原的血清学描述一致。编码B76抗原的一个等位基因（B*1512）似乎是HLA-A和-B基因座之间基因转换的产物，与B*1501的密码子166和167不同。相反，编码B76抗原的第二个等位基因（B*1514）与B*1501的不同之处在于密码子167中的一个不相关的取代，该取代与B45类似，是一种与B76交叉反应的抗原。编码B76的第三个等位基因B*1519与B*1512的不同之处在于外显子4中的独特点取代。编码变异体B15和B62抗原的三个等位基因（B*1508、B*1511和B*1515）与B*1501的不同之处在于可能由等位基因间转换引起的局部簇取代。本文中描述的B15序列，结合先前确定的那些，定义了一个22个等位基因的家族，包括编码B46和B70抗原的那些。在该家族中，等位基因取代的模式与其他HLA-A和-B家族的模式相似，因为成对差异几乎总是涉及抗原识别位点的功能位置，重组是多样化的主要因素。
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 (B*1517) and 8w66 (B*1516) heavy chains have sequence identity to B17 in the alpha1 helix correlating with the antigenic crossreactivity of these molecules. HLA-B77(B*1513) and B75 (B*1502) 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 (B*1512) appears to be the product of gene conversion between the HLA-A and -B loci and differs from B*1501 in codons 166 and 167. In contrast, a second allele encoding the B76 antigen (B*1514) differs from B*1501 by an unrelated substitution in codon 167 which confers similarily with B45, an antigen crossreactive with B76. A third allele encoding B76, B*1519, differs from B*1512 by a unique point substitution in exon 4. Three alleles encoding variant B15 and B62 antigens (B*1508, B*1511 and B*1515) differ from B*1501 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.