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恒河猴免疫球蛋白IGHD和IGHJ种系基因库。

The Rhesus monkey immunoglobulin IGHD and IGHJ germline repertoire.

作者信息

Link Jason M, Hellinger Matthew A, Schroeder Harry W

机构信息

Division of Developmental and Clinical Immunology, Department of Microbiology, University of Alabama at Birmingham, AL 35294-3300, USA.

出版信息

Immunogenetics. 2002 Jul;54(4):240-50. doi: 10.1007/s00251-002-0468-2. Epub 2002 Jun 14.

DOI:10.1007/s00251-002-0468-2
PMID:12136335
Abstract

In order to facilitate molecular analysis of antibody responses in Rhesus monkeys ( Macaca mulatta), we used PCR techniques to clone and sequence the germline IGHD gene repertoire and the IGHD7- IGHJ6 locus in its entirety. We identified 30 distinct Rhesus DH genes belonging to seven subgroups and their recombination signal sequences that together share an average of 91% identity with their human counterparts, six potentially functional IGHJ genes and their recombination signal sequences that together share 93% identity with their human counterparts, as well as a novel IGHJ gene, IGHJ5 beta, which is a duplicated variant of IGHJ5. The presence, on average, of one additional IGHD gene in Rhesus IGHD subgroups when compared with human and one additional IGHJ gene suggests Rhesus has undergone at least two independent duplications beyond those that mark the human IGHD/IGHJ locus. Amino acid sequence composition is highly conserved between Rhesus and human, with IGHD insertions and deletions limited to three-nucleotide multiples, which serve to preserve enrichment for tyrosine, glycine, and serine residues in IGHD reading frame 1. The high degree of conservation between human and Rhesus IGHD and IGHJ genes supports the hypothesis that the germline repertoire encodes evolutionarily preferred antibody sequence as a result of selection for function.

摘要

为了便于对恒河猴(猕猴)的抗体反应进行分子分析,我们使用聚合酶链反应(PCR)技术对种系免疫球蛋白重链多样性(IGHD)基因库以及完整的IGHD7-IGHJ6基因座进行克隆和测序。我们鉴定出30个不同的恒河猴多样性重链(DH)基因,它们属于七个亚组及其重组信号序列,这些序列与人类对应序列的平均同源性为91%;六个潜在功能性免疫球蛋白重链连接(IGHJ)基因及其重组信号序列,与人类对应序列的同源性为93%;还有一个新的IGHJ基因,IGHJ5β,它是IGHJ5的重复变体。与人类相比,恒河猴IGHD亚组平均多一个IGHD基因,且多一个IGHJ基因,这表明恒河猴在标记人类IGHD/IGHJ基因座的重复之外至少经历了两次独立的重复。恒河猴和人类之间的氨基酸序列组成高度保守,IGHD的插入和缺失仅限于三个核苷酸的倍数,这有助于在IGHD阅读框1中保持酪氨酸、甘氨酸和丝氨酸残基的富集。人类和恒河猴IGHD及IGHJ基因之间的高度保守支持了这样一种假设,即种系基因库通过功能选择编码进化上优选的抗体序列。

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