T cell receptor convergence is an indicator of antigen-specific T cell response in cancer immunotherapies
T cells are potent at eliminating pathogens and playing a crucial role in the adaptive immune response. T cell receptor (TCR) convergence describes T cells that share identical TCRs with the same amino acid sequences but have different DNA sequences due to codon degeneracy. We conducted a systematic investigation of TCR convergence using single-cell immune profiling and bulk TCRβ-sequence (TCR-seq) data obtained from both mouse and human samples, and uncovered a strong link between antigen-specificity and convergence. This association was stronger than T cell expansion, a putative indicator of antigen-specific T cells. By using flow sorted tetramer+ single T cell data, we discovered that convergent T cells were enriched for a neoantigen-specific CD8+ effector phenotype in the tumor microenvironment. Moreover, TCR convergence demonstrated better prediction accuracy for immunotherapy response than the existing TCR repertoire indexes. In conclusion, convergent T cells are likely to be antigen-specific and might be a novel prognostic biomarker for anti-cancer immunotherapy.
All data used in this work are publicly available. The Python code related to TCR convergence calculation are availableat:https://github.com/Mia-yao/TCR-convergence/tree/main. The convergent TCR sequences of each cohort are uploaded to Zenodo, with DOI: 10.5281/zenodo.6603757.
A large-scale database of T-cell receptor beta (TCRβ) sequences and binding associations from natural and synthetic exposure to SARS-CoV-2immuneAccess: https://doi.org/10.21417/ADPT2020COVID.
Article and author information
National Cancer Institute (1R01CA245318)
- Bo Li
National Cancer Institute (1R01CA258524)
- Bo Li
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Kellie N Smith, The Johns Hopkins University School of Medicine, United States
- Preprint posted: June 16, 2022 (view preprint)
- Received: July 18, 2022
- Accepted: November 8, 2022
- Accepted Manuscript published: November 9, 2022 (version 1)
- Version of Record published: November 23, 2022 (version 2)
© 2022, Pan & Li
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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