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一种新世界灵长类物种棉顶狨的T细胞受体β链编码基因库。

The T-cell receptor beta chain-encoding gene repertoire of a New World primate species, the cotton-top tamarin.

作者信息

Allen T M, Lanchbury J S, Hughes A L, Watkins D I

机构信息

Wisconsin Regional Primate Research Center, University of Wisconsin, 1220 Capitol Court, Madison, WI 53715, USA.

出版信息

Immunogenetics. 1996;45(2):151-60. doi: 10.1007/s002510050183.

Abstract

The New World primate, the cotton-top tamarin (Saguinus oedipus), expresses major histocompatibility complex (MHC) class I molecules with limited diversity. The uniqueness of the cotton-top tamarin MHC class I loci may contribute to this species' unusual susceptibility to viral infections and high incidence of ulcerative colitis. As a prelude to examining the effect of this limited MHC class I diversity on the tamarin CD8(+) T-cell receptor (TCR) repertoire, we identified expressed tamarin TCR beta chain (TCRB) cDNAs by anchored and inverse polymerase chain reaction. Sequence alignments and phylogenetic comparisons with human and rhesus macaque sequences identified homologues of 21 human variable (V) gene families. Only single variable region genes were identified in each of these tamarin VB families, with the exception of the VB 5, 9, and 13 families which were comprised of two or three distinct members. The multiple genes within these three VB families do not appear to have separate human homologues, but rather aligned equally well to a single human gene from their respective VB families. These genes appear to have arisen, therefore, by duplication of certain VB genes in the tamarin ancestors following their divergence from the lineage leading to Old World primates and hominoids. Homologues of 12 of the 13 human joining (J) region genes were also identified in the tamarin. Comparison of the proportion of nonsynonymous (pN) and synonymous (pS) substitutions occurring per site within tamarin variable region genes demonstrated a reduction in pN in the framework regions compared with pN in the presumed MHC contact regions (CDR1 and CDR2). Taken together, these findings illustrate that the TCR beta chain-encoding genes of the cotton-top tamarin are similar in structure and degree of complexity compared with their Old World primate and human counterparts.

摘要

新大陆灵长类动物棉顶狨(Saguinus oedipus)表达的主要组织相容性复合体(MHC)I类分子具有有限的多样性。棉顶狨MHC I类基因座的独特性可能导致该物种对病毒感染异常易感以及溃疡性结肠炎的高发病率。作为研究这种有限的MHC I类多样性对狨猴CD8(+) T细胞受体(TCR)库影响的前奏,我们通过锚定和反向聚合酶链反应鉴定了表达的狨猴TCRβ链(TCRB)cDNA。与人类和恒河猴序列的序列比对及系统发育比较确定了21个人类可变(V)基因家族的同源物。在这些狨猴VB家族中,每个家族仅鉴定出单个可变区基因,但VB 5、9和13家族除外,它们由两个或三个不同成员组成。这三个VB家族中的多个基因似乎没有单独的人类同源物,而是与来自各自VB家族的单个人类基因具有同样好的比对。因此,这些基因似乎是在狨猴祖先与导致旧大陆灵长类动物和类人猿的谱系分化后,通过某些VB基因的复制而产生的。在狨猴中还鉴定出了13个人类连接(J)区基因中的12个的同源物。狨猴可变区基因内每个位点发生的非同义(pN)和同义(pS)替换比例的比较表明,与假定的MHC接触区域(CDR1和CDR2)中的pN相比,框架区域中的pN有所降低。综上所述,这些发现表明,棉顶狨编码TCRβ链的基因在结构和复杂程度上与其旧大陆灵长类动物和人类对应物相似。

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