Genesis of the T-cell receptor
Genesis of the T-cell receptor
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DOI：
10.1371/journal.pcbi.1006874
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发表时间：
2019-03-01
影响因子：
4.3
通讯作者：
Mora, Thierry
中科院分区：
文献类型：
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作者：
Dupic, Thomas;Marcou, Quentin;Mora, Thierry
T细胞（TCR）库依赖于由两条链组成的受体的多样性，称为和，以识别病原体。使用人类TCR库的高通量测序和计算链配对实验的结果，我们定量表征生成过程。我们估计了在第一条染色体上失败或成功后，第二条染色体上的链的拯救重组的概率。与链不同，链在两条染色体上同时重组，导致我们使用机械模型预测的两个基因的相关统计。我们发现，大约35%的细胞表达这两种链。总之，我们的统计分析给出了一个完整的定量机制的图片，在生成过程中观察到的相关性的结果。我们了解到产生任何TCR的概率低于10（-12），并估计了TCR库的世代多样性和共享特性。作者摘要T细胞表面的受体识别病原体并启动免疫应答。分析人类T细胞受体的序列，我们绘制了两个受体链的生成过程的详细定量图，使我们能够估计完整库的多样性。我们讨论了哪些元素的受体生产过程是相关的，哪些是独立的，提出了机械模型的相关性的起源。我们讨论了我们的研究结果的影响，这些细胞中的每一个的功能作用，和剧目的多样性。
The T-cell (TCR) repertoire relies on the diversity of receptors composed of two chains, called and , to recognize pathogens. Using results of high throughput sequencing and computational chain-pairing experiments of human TCR repertoires, we quantitively characterize the generation process. We estimate the probabilities of a rescue recombination of the chain on the second chromosome upon failure or success on the first chromosome. Unlike chains, chains recombine simultaneously on both chromosomes, resulting in correlated statistics of the two genes which we predict using a mechanistic model. We find that approximate to 35% of cells express both chains. Altogether, our statistical analysis gives a complete quantitative mechanistic picture that results in the observed correlations in the generative process. We learn that the probability to generate any TCR is lower than 10(-12) and estimate the generation diversity and sharing properties of the TCR repertoire.Author summary Receptors on the surface of T-cells recognize pathogens and initiate an immune response. Analyzing the sequences of human T-cell receptors we draw a detailed quantitative picture of the generation process of the two receptor chains allowing us to estimate the diversity of the complete repertoire. We discuss which elements of the receptor production processes are correlated and which are independent, proposing mechanistic models at the origin of the correlations. We discuss the implications of our findings for the functional role of each of these cells, and the diversity of the repertoire.