High-throughput pairing of T cell receptor α and β sequences
High-throughput pairing of T cell receptor α and β sequences
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DOI：
10.1126/scitranslmed.aac5624
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发表时间：
2015-08-19
影响因子：
17.1
通讯作者：
Robins, Harlan S.
中科院分区：
文献类型：
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作者：
Howie, Bryan;Sherwood, Anna M.;Robins, Harlan S.
T细胞受体（TCR）蛋白是由α链和β链组成的异二聚体。TCR基因经历体细胞DNA重排以产生有效免疫所需的T细胞结合特异性的多样性。最近，已经开发了高通量免疫测序方法来分析TCR α（TCRA）和TCR β（TCRB）谱系。然而，这些方法不能确定哪一个TCRA和TCRB链联合收割机组合形成特异性TCR，这对于许多功能和治疗应用是必需的。我们描述并验证了一种称为pairSEQ的方法，该方法可以利用TCR序列的多样性，在一个实验中准确地配对数十万个TCRA和TCRB序列。我们的TCR配对方法使用标准实验室耗材和设备，无需单细胞技术。我们表明，pairSEQ可以应用于血液和实体组织，如肿瘤的T细胞。
The T cell receptor (TCR) protein is a heterodimer composed of an alpha chain and a beta chain. TCR genes undergo somatic DNA rearrangements to generate the diversity of T cell binding specificities needed for effective immunity. Recently, high-throughput immunosequencing methods have been developed to profile the TCR alpha (TCRA) and TCR beta (TCRB) repertoires. However, these methods cannot determine which TCRA and TCRB chains combine to form a specific TCR, which is essential for many functional and therapeutic applications. We describe and validate a method called pairSEQ, which can leverage the diversity of TCR sequences to accurately pair hundreds of thousands of TCRA and TCRB sequences in a single experiment. Our TCR pairing method uses standard laboratory consumables and equipment without the need for single-cell technologies. We show that pairSEQ can be applied to T cells from both blood and solid tissues, such as tumors.