The naive T-cell receptor repertoire has an extremely broad distribution of clone sizes
The naive T-cell receptor repertoire has an extremely broad distribution of clone sizes
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DOI：
10.7554/elife.49900
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发表时间：
2020-03-18
期刊：
影响因子：
7.7
通讯作者：
de Boer, Rob J.
中科院分区：
文献类型：
--
作者：
de Greef, Peter C.;Oakes, Theres;de Boer, Rob J.
人类幼稚t细胞受体（TCR）库的克隆大小分布是适应性免疫的重要决定因素。我们使用精确的定量测序方案估计了血液中幼稚T细胞样本中TCR序列的丰度。我们只观察到大多数TCR序列一次，这与该序列的巨大多样性是一致的。然而，大量的序列被观察了多次。我们检测到大量的TCR序列，即使在排除了方法混杂因素（如排序污染）和来自同一细胞的多个mRNA采样之后。通过将实验数据与模型预测相结合，我们描述了两种促进TCR序列丰度的机制。丰富的TCR α序列主要归因于不同细胞中许多相同的重组事件，而丰富的TCR β序列主要来源于大型克隆，这些克隆只占初始库的一小部分，并且可以在t细胞库的早期发展中建立。
The clone size distribution of the human naive T-cell receptor (TCR) repertoire is an important determinant of adaptive immunity. We estimated the abundance of TCR sequences in samples of naive T cells from blood using an accurate quantitative sequencing protocol. We observe most TCR sequences only once, consistent with the enormous diversity of the repertoire. However, a substantial number of sequences were observed multiple times. We detect abundant TCR sequences even after exclusion of methodological confounders such as sort contamination, and multiple mRNA sampling from the same cell. By combining experimental data with predictions from models we describe two mechanisms contributing to TCR sequence abundance. TCR alpha abundant sequences can be primarily attributed to many identical recombination events in different cells, while abundant TCR beta sequences are primarily derived from large clones, which make up a small percentage of the naive repertoire, and could be established early in the development of the T-cell repertoire.