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

B Howie, AM Sherwood, AD Berkebile… - Science translational …, 2015 - science.org
B Howie, AM Sherwood, AD Berkebile, J Berka, RO Emerson, DW Williamson, I Kirsch
Science translational medicine, 2015science.org
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 …
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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