Candéias S, Waltzinger C, Benoist C, Mathis D
Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, l'INSERM, Strasbourg, France.
J Exp Med. 1991 Nov 1;174(5):989-1000. doi: 10.1084/jem.174.5.989.
To ascertain how the actual repertoire of T cell receptors (TCRs) deviates from the theoretical, we have generated a large number of junctional region sequences from TCRs carrying the V beta 17 variable region. The greater than 600 sequences analyzed represent transcripts from nine different cell populations, permitting several comparisons: transcripts from an expressed vs. a non-expressed V beta 17 allele, those from E+ vs. E- mice, transcripts from immature vs. mature thymocytes, those from thymic vs. peripheral T cells, and those from CD4+ vs. CD8+ cells. These comparisons have allowed us to distinguish between the influence of molecular events involved in TCR gene rearrangement and that of various selection events that shape the T cell repertoire. Our most striking findings are: (a) that J beta usage is markedly skewed, partly due to recombination mechanics and partly due to selection forces: in particular, those mediated by the class II E molecule in the thymus; and (b) that TCRs on CD4+ and CD8+ cells show intriguing dissimilarities. In addition, we present evidence that N nucleotide additions occur with clear biases, probably due to idiosyncrasies of the recombination enzymes, and provide arguments that TCR and immunoglobulin CDR3s have distinct structures.
为了确定T细胞受体（TCR）的实际库如何偏离理论情况，我们从携带Vβ17可变区的TCR中生成了大量连接区序列。所分析的600多个序列代表了来自9种不同细胞群体的转录本，从而可以进行多种比较：来自表达的与未表达的Vβ17等位基因的转录本、来自E +小鼠与E -小鼠的转录本、来自未成熟与成熟胸腺细胞的转录本、来自胸腺T细胞与外周T细胞的转录本，以及来自CD4 +细胞与CD8 +细胞的转录本。这些比较使我们能够区分TCR基因重排中涉及的分子事件的影响与塑造T细胞库的各种选择事件的影响。我们最显著的发现是：（a）Jβ的使用明显偏向，部分是由于重组机制，部分是由于选择力，特别是胸腺中II类E分子介导的选择力；（b）CD4 +和CD8 +细胞上的TCR表现出有趣的差异。此外，我们提供的证据表明，N核苷酸的添加存在明显偏差，这可能是由于重组酶的特性所致，并论证了TCR和免疫球蛋白的互补决定区3（CDR3）具有不同的结构。
