STRUCTURE, DIVERSITY, AND EVOLUTION OF THE T-CELL RECEPTOR VB GENE REPERTOIRE IN PRIMATES

STRUCTURE, DIVERSITY, AND EVOLUTION OF THE T-CELL RECEPTOR VB GENE REPERTOIRE IN PRIMATES
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DOI:
10.1007/bf00167078
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发表时间:
1994-07-01
期刊:
影响因子:
3.2
通讯作者:
LANCHBURY, JS
LANCHBURY, JS
中科院分区:
医学4区
文献类型:
--
作者:
JAEGER, EEM;BONTROP, RE;LANCHBURY, JS

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识别主要组织相容性复合体(MHC)/多肽抗原复合体的AB T细胞受体(TCR)调节适应性免疫反应的体液和细胞臂。MHC和免疫球蛋白重链可变区(IgH-V)的抗原结合部位受到多样性增强选择的影响。我们试图通过对猕猴和黑猩猩重新排列的TCR进行测序,并将其与人类的TCRBV链进行比较,来确定积极的达尔文选择是否推动了灵长类TCRBV链的多样性。同义(沉默)和非同义(替换)替换的比率表明,针对TCRBV框架中的氨基酸替换进行了选择,并在假定的MHC/肽接触部位放松了这些限制。在可能的配体接触部位缺乏对变异性的正选择,这表明在TCR连接区产生体细胞多样性的机制缓解了在生殖系编码的TCR V区对变异性的选择压力。
AB T-cell receptors (TCR) that recognize major histocompatibility complex (MHC)/peptide antigen complexes regulate humoral and cellular arms of the adaptive immune response. Antigen binding sites of MHC and immunoglobulin heavy chain variable regions (Igh-V) are subject to diversity enhancing selection. We sought to establish whether positive Darwinian selection has driven diversity of TCRBV chains in the primate lineage by sequencing rearranged TCR from rhesus monkeys and chimpanzees and comparing them with those of humans. Rates of synonymous (silent) and nonsynonymous (replacement) substitutions indicate selection against amino acid replacements in TCRBV frameworks, and relaxation of these constraints in putative MHC/peptide contact sites. The lack of positive selection for variability in likely ligand contact sites suggests that mechanisms generating somatic diversity in TCR junctional regions have relaxed the pressure for selection of variability in the TCR V region encoded in the germline.