Influence of coding region polymorphism on the peripheral expression of a human TCR V beta gene.
Influence of coding region polymorphism on the peripheral expression of a human TCR V beta gene.
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DOI：
10.4049/jimmunol.152.3.1222
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发表时间：
1994-02
影响因子：
4.4
通讯作者：
C. Vissinga;P. Charmley;P. Concannon
中科院分区：
文献类型：
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作者：
C. Vissinga;P. Charmley;P. Concannon
据报道，许多人TCR V β基因片段是多态性的，等位基因的差异在于一个或少量氨基酸取代。在缺乏关于TCR中特定位置与Ag或MHC的相互作用的详细结构信息的情况下，难以评估这种变化的意义。在本报告中，在来源于这些等位基因杂合子个体的PBL中测量了人类V β 6.7基因的两个常见等位基因6.7a和6.7b的相对使用，这两个等位基因的差异在于两个非保守氨基酸取代，以及V β 12.2基因的两个常见等位基因的使用，这两个等位基因的差异在于沉默取代。观察到V β 12.2等位基因的同等使用，这与选择机制无法区分在氨基酸水平上无法区分的这些等位基因的产物一致。然而，在研究的16个个体中，有15个个体观察到V β 6.7等位基因的使用存在统计学显著的偏斜。在杂合子个体中，每个等位基因的表达水平范围为总V β 6.7信号的16%至84%，在不同个体中，6.7a或6.7b等位基因占主导地位。基于在家族中的分离研究，TCR β基因座中的其他未鉴定的多态性，例如V β 6.7启动子，似乎不太可能是差异等位基因表达的原因。家族研究未提供特定HLA单倍型与V β 6.7等位基因使用之间存在关联的证据。这些结果表明，即使人TCR V β编码区中的适度等位基因变异也可对外周库中人V β基因的表达具有显著影响。
A number of human TCR V beta gene segments are reported to be polymorphic, with alleles differing by one or a small number of amino acid substitutions. In the absence of detailed structural information regarding the interaction of specific positions in the TCR with Ag or MHC, the significance of such variation is difficult to assess. In this report the relative use of the two common alleles of the human V beta 6.7 gene, 6.7a and 6.7b, which differ by two non-conservative amino acid substitutions, and the use of two common alleles of the V beta 12.2 gene, which differ by only silent substitutions, were measured in PBL derived from individuals heterozygous for these alleles. Equal use of V beta 12.2 alleles was observed, consistent with the inability of selection mechanisms to discriminate between the products of these alleles that are indistinguishable at the amino acid level. However, statistically significant skewing in the use of V beta 6.7 alleles was observed in 15 of 16 individuals studied. Expression levels for each allele ranged from 16 to 84% of the total V beta 6.7 signal in heterozygous individuals, with either the 6.7a or the 6.7b allele predominant in different individuals. Based on segregation studies in families, it seems unlikely that other unidentified polymorphism in the TCR beta locus, such as in the V beta 6.7 promoter, was responsible for the differential allele expression. Family studies provided no evidence for an association between specific HLA haplotypes and V beta 6.7 allele use. These results indicate that even modest allelic variation in human TCR V beta coding regions can have a significant impact on the expression of human V beta genes in the peripheral repertoire.