Deep sequencing of the T cell receptor β repertoire reveals signature patterns and clonal drift in atherosclerotic plaques and patients.
Deep sequencing of the T cell receptor β repertoire reveals signature patterns and clonal drift in atherosclerotic plaques and patients.
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T 细胞受体 β 库的深度测序揭示了动脉粥样硬化斑块和患者的特征模式和克隆漂移
DOI：
10.18632/oncotarget.19892
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发表时间：
2017-11-21
期刊：
影响因子：
--
通讯作者：
Zhang Q
中科院分区：
文献类型：
--
作者：
Lin Z;Qian S;Gong Y;Ren J;Zhao L;Wang D;Wang X;Zhang Y;Wang Z;Zhang Q
T细胞受体（TCR）β库直接反映T细胞功能状态。同时，T细胞调节的免疫/炎症反应是动脉粥样硬化发展的关键决定因素。然而，由于技术限制，动脉粥样硬化患者TCR库的组成和分子特征尚未完全阐明。在本研究中，我们利用强大的免疫组库测序技术来研究这个问题。结果显示，与正常人和动脉粥样硬化患者的外周血相比，动脉粥样硬化斑块中V和/或J基因的利用率和TCRβ库的多样性显着降低。具有一定长度的补体决定区3区域的常见T细胞克隆的频率在所有组中显着不同。与其他两组相比，动脉粥样硬化斑块中的高频共同克隆也有所增加。几种 T 细胞克隆型（V29-1J2-1、V20-1J1-6、V6-3J2-7 和 V11-2J2-2）的扩增在动脉粥样硬化患者中得到验证。简而言之，这项研究揭示了动脉粥样硬化斑块中 TCR β 库的多样性显着降低，这可能是由于 VJ 基因的利用减少和一些 T 细胞亚克隆的显着扩张所致。它为理解T淋巴细胞在动脉粥样硬化发病机制中的作用提供了基础。
The T cell receptor (TCR) β repertoire directly reflects the status of T cell function. Meanwhile, the immune/inflammatory responses regulated by T cells are the critical determinants of atherosclerosis development. However, due to technical limitations, the composition and molecular characteristics of the TCR repertoire in atherosclerotic patients have not been fully elucidated. In the present study, we use powerful immune repertoire sequencing technology to study this issue. Results show that the utilization of V and/or J genes and the diversity of TCRβ repertoire in atherosclerotic plaques are significantly reduced compared to those in the peripheral blood of normal subjects and atherosclerotic patients. The frequencies of the common T cell clones with certain lengths of the complement determining region 3 regions are notably different among all groups. The high-frequency common clones are also increased in the atherosclerotic plaques compared to that in the other two groups. The expansion of several T cell clonotypes (V29-1J2-1, V20-1J1-6, V6-3J2-7 and V11-2J2-2) is validated in atherosclerotic patients. In short, this study reveals that the diversity of TCR β repertoire significantly decreases in atherosclerotic plaques, probably because of the reduced utilization of VJ genes and marked expansion of some T cell subclones. It provides the basis for understanding the roles of T lymphocytes in the pathogenesis of atherosclerosis.
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