Research ArticleImmunology

High-throughput pairing of T cell receptor α and β sequences

Science Translational Medicine  19 Aug 2015:
Vol. 7, Issue 301, pp. 301ra131
DOI: 10.1126/scitranslmed.aac5624

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T cell receptor chains pair off

High-throughput immunosequencing can take a snapshot of the repertoire of immune cells, providing a broad picture of the immune response at any given time and tracking how the immune response changes as a result of perturbations such as vaccines, infection, or cancer. However, this approach has been limited by the inability to determine which TCR α and TCR β chains combine to form specific T cell receptors in a given cell. Now, Howie et al. report and validate a high-throughput method to pair TCR α and β segments without the need for single-cell technologies. They confirm that their method can be used for T cells from both blood and solid tissues.

Abstract

The T cell receptor (TCR) protein is a heterodimer composed of an α chain and a β 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 α (TCRA) and TCR β (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.

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