T cell receptor convergence is an indicator of antigen-specific T cell response in cancer immunotherapies.

Abstract

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.

• Authors: Mingyao Pan, Bo Li
• Journal: eLife (Elife) Vol. 11 (11 09 2022) ISSN: 2050-084X [Electronic] England
• PMID: 36350695 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2022, Pan and Li.

Chemical References

• Receptors, Antigen, T-Cell

Topics

• Humans
• Mice
• Animals
• T-Lymphocytes
• Receptors, Antigen, T-Cell (metabolism)
• Immunotherapy
• Amino Acid Sequence
• Neoplasms (therapy)