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

Shu-Qi Zhang1,7, Ke-Yue Ma2,7, Alexandra A Schonnesen3,7, Mingliang Zhang4,5,7, Chenfeng He3, Eric Sun3, Chad M Williams3, Weiping Jia4,5 & Ning Jiang2,3,6

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 tetrameters 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 wildtype antigen.

Nature Biotechnology, published online 12 November 2018