Jouvin-Marche Evelyne, Fuschiotti Patrizia, Marche Patrice Noël
Université Joseph Fourier-Grenoble I, Faculté de Médecine, Institut d'Oncologie/Developpement Albert Bonniot et Institut Français du Sang, UMR-S823, Grenoble, France.
Adv Exp Med Biol. 2009;650:82-92. doi: 10.1007/978-1-4419-0296-2_7.
Most T-lymphocytes express a highly specific antigen receptor (TCR) on their cell surface, consisting of a clonotypic alphabeta-heterodimer. Both alpha- and beta chains are products of somatic rearrangements of V, (D) and J gene segments encoded on the respective loci. The qualitative, quantitative and dynamic aspects of the TCRalpha chain repertoire of humans and mice have been difficult to estimate, mainly due to locus complexity. Analyses of the T-cell repertoire were first performed at the transcriptional level using classical cloning and sequencing strategies and then later at the genomic level using sensitive multiplex PCR assays that allow surveying the global rearrangement of the TCRAD locus. These all converge and support the conclusion that the V-J recombination pattern in both human and mouse thymus is not random but depends on the reciprocal V and J positions within the locus, thereby limiting the combinatorial diversity of the TCRalpha chain repertoire. The recombination profile is compatible with a sequential opening of the V region with progressive tracking along the two regions in opposite directions starting from the nearest and then moving towards the most distant V and J gene segments. In this chapter, we report new insights into the degree of human and mouse TCRalpha chain diversity in thymic and peripheral T-lymphocytes. Since the comparison of human and mouse V-J recombination shows a similar pattern of rearrangement, we suggest that spatial and temporal synchronization on the accessibility of V and J gene segments are general features of V-J rearrangements that are conserved throughout evolution.
大多数T淋巴细胞在其细胞表面表达一种高度特异性的抗原受体（TCR），它由一个克隆型αβ异二聚体组成。α链和β链都是各自基因座上编码的V、（D）和J基因片段进行体细胞重排的产物。由于基因座的复杂性，人类和小鼠TCRα链库的定性、定量和动态方面一直难以评估。对T细胞库的分析首先在转录水平上使用经典的克隆和测序策略进行，随后在基因组水平上使用灵敏的多重PCR检测方法进行，这种方法能够检测TCRAD基因座的整体重排情况。这些分析都得出并支持这样的结论：人类和小鼠胸腺中的V-J重组模式并非随机，而是取决于基因座内V和J的相对位置，从而限制了TCRα链库的组合多样性。这种重组模式与V区域的顺序开放相一致，即从最近的V和J基因片段开始，沿两个区域以相反方向逐步追踪。在本章中，我们报告了对人类和小鼠胸腺及外周T淋巴细胞中TCRα链多样性程度的新见解。由于人类和小鼠V-J重组的比较显示出相似的重排模式，我们认为V和J基因片段可及性的时空同步是V-J重排的普遍特征，在整个进化过程中都是保守的。
