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.


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.