A highly diverse repertoire of T cell antigen receptors (TCR) is created in the thymus by recombination of gene segments and the insertion or deletion of nucleotides at the junctions. Using next-generation TCR sequencing we define here the features of recombination and selection in the human TCRα and TCRβ locus, and show that a strikingly high proportion of the repertoire is shared by unrelated individuals. The thymic TCRα nucleotide repertoire was more diverse than TCRβ, with 4.1 × 10⁶ vs. 0.81 × 10⁶ unique clonotypes, and contained nonproductive clonotypes at a higher frequency (69.2% vs. 21.2%). The convergence of distinct nucleotide clonotypes to the same amino acid sequences was higher in TCRα than in TCRβ repertoire (1.45 vs. 1.06 nucleotide sequences per amino acid sequence in thymus). The gene segment usage was biased, and generally all individuals favored the same genes in both TCRα and TCRβ loci. Despite the high diversity, a large fraction of the repertoire was found in more than one donor. The shared fraction was bigger in TCRα than TCRβ repertoire, and more common in in-frame sequences than in nonproductive sequences. Thus, both biases in rearrangement and thymic selection are likely to contribute to the generation of shared repertoire in humans.

通过基因片段的重组以及连接处核苷酸的插入或缺失，在胸腺中产生了高度多样化的T细胞抗原受体（TCR）库。使用下一代TCR测序，我们在此处定义了人TCRα和TCRβ基因座中重组和选择的特征，并显示出极高比例的曲目被无关的个人共享。胸腺TCRα核苷酸的组成比TCRβ更多样化，分别为4.1×10 ⁶和0.81×10 ⁶独特的克隆型，并包含较高频率的非生产性克隆型（69.2％对21.2％）。在TCRα中，不同的核苷酸克隆型向相同氨基酸序列的收敛高于在TCRβ库中（胸腺中每个氨基酸序列分别为1.45对1.06个核苷酸序列）。基因片段的使用是有偏见的，通常所有个体都在TCRα和TCRβ基因座中偏爱相同的基因。尽管多样性很高，但在超过一个捐赠者中发现了大部分曲目。在TCRα中，共有分数大于TCRβ组成部分，并且在框内序列中比在非生产性序列中更常见。因此，重排和胸腺选择的偏倚都可能有助于人类共享曲目的产生。