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Sci Transl Med. 2015 Aug 19;7(301):301ra131. doi: 10.1126/scitranslmed.aac5624.

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

Author information

1
Adaptive Biotechnologies, Seattle, WA 98102, USA.
2
Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
3
Adaptive Biotechnologies, Seattle, WA 98102, USA. Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. hrobins@fredhutch.org.

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.

PMID:
26290413
DOI:
10.1126/scitranslmed.aac5624
[Indexed for MEDLINE]

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