论文标题
T细胞库的产生和胸腺选择的人群变异性
Population variability in the generation and thymic selection of T-cell repertoires
论文作者
论文摘要
T细胞受体(TCR)曲目的多样性是通过两个本质上随机的步骤的组合来实现的:通过VDJ重组产生随机受体,以及基于对主要组织相容性复合物中介绍的随机自肽的识别的选择。这些过程导致个体内部和个体之间的较大受体变异性。但是,可变性的表征受到采样库的有限尺寸的阻碍。我们引入了一种新的软件工具SONIA,以促进从651个个人的测序曲目中的生成和选择TCR Beta链(TRB)的个人特定计算模型,从而分离和量化了人群中两个生成和选择过程的变化。我们不仅发现大多数可变性是由VDJ生成过程驱动的,而且具有个人间差异的个体差异约为个体内部差异的2%之间存在很大程度的一致性。已知的病毒特异性TCR遵循与所有TCR相同的一代和选择统计。
The diversity of T-cell receptor (TCR) repertoires is achieved by a combination of two intrinsically stochastic steps: random receptor generation by VDJ recombination, and selection based on the recognition of random self-peptides presented on the major histocompatibility complex. These processes lead to a large receptor variability within and between individuals. However, the characterization of the variability is hampered by the limited size of the sampled repertoires. We introduce a new software tool SONIA to facilitate inference of individual-specific computational models for the generation and selection of the TCR beta chain (TRB) from sequenced repertoires of 651 individuals, separating and quantifying the variability of the two processes of generation and selection in the population. We find not only that most of the variability is driven by the VDJ generation process, but there is a large degree of consistency between individuals with the inter-individual variance of repertoires being about 2% of the intra-individual variance. Known viral-specific TCRs follow the same generation and selection statistics as all TCRs.