High-throughput determination of the antigen specificities of T cell receptors in single cells

Shu-Qi Zhang; Ke-Yue Ma; Alexandra A Schonnesen; Mingliang Zhang; Chenfeng He; Eric Sun; Chad M Williams; Weiping Jia; Ning Jiang

doi:10.1038/nbt.4282

High-throughput determination of the antigen specificities of T cell receptors in single cells

Nat Biotechnol. 2018 Nov 12:10.1038/nbt.4282. doi: 10.1038/nbt.4282. Online ahead of print.

Authors

Shu-Qi Zhang¹, Ke-Yue Ma², Alexandra A Schonnesen³, Mingliang Zhang^{4

5}, Chenfeng He³, Eric Sun³, Chad M Williams³, Weiping Jia^{4

5}, Ning Jiang^{2

3

6}

Affiliations

¹ McKetta Department of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA.
² Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas, USA.
³ Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas, USA.
⁴ Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
⁵ Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center of Diabetes, Shanghai, China.
⁶ LIVESTRONG Cancer Institutes, Dell Medical School, University of Texas at Austin, Austin, Texas, USA.

Abstract

We present tetramer-associated T-cell receptor sequencing (TetTCR-seq) to link T cell receptor (TCR) sequences to their cognate antigens in single cells at high throughput. Binding is determined using a library of DNA-barcoded antigen tetramers that is rapidly generated by in vitro transcription and translation. We applied TetTCR-seq to identify patterns in TCR cross-reactivity with cancer neoantigens and to rapidly isolate neoantigen-specific TCRs with no cross-reactivity to the wild-type antigen.

Abstract

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