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bioRxivImmunology

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

S.-Q. Zhang, K.-Y. Ma, A. A. Schonnesen, M. Zhang, C. He, E. Sun, C. M. Williams, W. Jia, N. Jiang

PDFDOIPreprint

Abstract

We present tetramer-associated T-cell receptor sequencing (TetTCR-Seq), a method 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 neo-antigens and to rapidly isolate neo-antigen-specific TCRs with no cross-reactivity to the wild-type antigen.

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