Reduced expression of a human V beta 6.1 T-cell receptor allele.
Reduced expression of a human V beta 6.1 T-cell receptor allele.
复制标题
人类 V beta 6.1 T 细胞受体等位基因的表达减少。
DOI：
10.1073/pnas.90.10.4369
复制
发表时间：
1993
影响因子：
11.1
通讯作者：
Glass,DN
中科院分区：
文献类型：
--
作者：
Luyrink,L;Gabriel,CA;Thompson,SD;Grom,AA;Maksymowych,WP;Choi,E;Glass,DN
我们先前已经描述了V β 6.1 T细胞受体基因的等位基因多态性。V β 6.1B等位基因与幼年类风湿关节炎患者亚组的疾病相关。有限的序列数据表明，核苷酸的差异，导致两个等位基因之间的位置预测是重要的主要组织相容性复合体/抗原识别的两个氨基酸的变化。本研究表明，在外周血和胸腺组织中，疾病相关等位基因（V β 6.1B）的mRNA表达显著降低。这两个等位基因的完整基因组序列揭示了V β 6.1B基因中的两个额外的氨基酸变化以及启动子和内含子中的核苷酸差异。在疾病相关等位基因中的位置92处的半胱氨酸至精氨酸的取代使其成为非功能性β链，因为该保守的半胱氨酸涉及与半胱氨酸-23的二硫键合以形成免疫球蛋白样结构域结构，从而导致T细胞受体库中的潜在孔。
We have previously described an allelic polymorphism in the V beta 6.1 T-cell receptor gene. The V beta 6.1B allele is associated with disease in a subgroup of patients with juvenile rheumatoid arthritis. Limited sequence data demonstrated nucleotide differences that resulted in two amino acid changes between the two alleles in positions predicted to be important in major histocompatibility complex/antigen recognition. The present study demonstrates substantially reduced expression of mRNA from the disease-associated allele (V beta 6.1B) in peripheral blood and thymic tissue. The complete genomic sequence of both alleles revealed two additional amino acid changes in the V beta 6.1B gene as well as nucleotide differences in the promoter and intron. A cysteine-to-arginine substitution at position 92 in the disease-associated allele makes this a non-functional beta chain, since this conserved cysteine is involved with disulfide bonding to cysteine-23 to form an immunoglobulin-like domain structure, thus resulting in a potential hole in the T-cell receptor repertoire.