High throughput sequencing reveals a complex pattern of dynamic interrelationships among human T cell subsets
High throughput sequencing reveals a complex pattern of dynamic interrelationships among human T cell subsets
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DOI：
10.1073/pnas.0913939107
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发表时间：
2010-01-26
影响因子：
11.1
通讯作者：
Han, Jian
中科院分区：
文献类型：
--
作者：
Wang, Chunlin;Sanders, Catherine M.;Han, Jian
发育中的T细胞在胸腺和外周面临一系列细胞命运的选择。个体T细胞受体(TCR)在决定细胞命运中的作用仍未解决。随机/选择模型假设细胞的初始命运与TCR的特异性无关，生存依赖于额外的TCR/辅助受体“救援”信号。“指导性”模型认为，细胞命运是由TCR与同源肽-MHC复合体相互作用启动的。然后，在关键的辅受体和信号调节剂的帮助下，根据T细胞受体的特异性分离T细胞[Chan S，Correia-Neves M，Benoist C，Mathis(1998)免疫修订版165：195-207]。前者将预测不同T细胞谱系中单个TCR的随机表现，而后者将预测不同T细胞亚群之间最小的重叠。为了解决这个问题，我们使用高通量测序来评估TCR在来自单一捐赠者的关键T细胞发育和效应亚群中的分布。我们发现了大量单个亚群共享相同TCR序列的例子，支持一个决定细胞命运的随机过程的模型，以及在CD4(+)和CD8+人群中携带相同TCR序列的T细胞克隆扩张的动态模式。
Developing T cells face a series of cell fate choices in the thymus and in the periphery. The role of the individual T cell receptor (TCR) in determining decisions of cell fate remains unresolved. The stochastic/selection model postulates that the initial fate of the cell is independent of TCR specificity, with survival dependent on additional TCR/coreceptor "rescue" signals. The "instructive" model holds that cell fate is initiated by the interaction of the TCR with a cognate peptide-MHC complex. T cells are then segregated on the basis of TCR specificity with the aid of critical coreceptors and signal modulators [Chan S, Correia-Neves M, Benoist C, Mathis (1998) Immunol Rev 165: 195-207]. The former would predict a random representation of individual TCR across divergent T cell lineages whereas the latter would predict minimal overlap between divergent T cell subsets. To address this issue, we have used high-throughput sequencing to evaluate the TCR distribution among key T cell developmental and effector subsets from a single donor. We found numerous examples of individual subsets sharing identical TCR sequence, supporting a model of a stochastic process of cell fate determination coupled with dynamic patterns of clonal expansion of T cells bearing the same TCR sequence among both CD4(+) and CD8+ populations.