Mapping the functional landscape of T cell receptor repertoires by single-T cell transcriptomics

Ze Zhang, Danyi Xiong, Xinlei Wang, Hongyu Liu, Tao Wang

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Many experimental and bioinformatics approaches have been developed to characterize the human T cell receptor (TCR) repertoire. However, the unknown functional relevance of TCR profiling hinders unbiased interpretation of the biology of T cells. To address this inadequacy, we developed tessa, a tool to integrate TCRs with gene expression of T cells to estimate the effect that TCRs confer on the phenotypes of T cells. Tessa leveraged techniques combining single-cell RNA-sequencing with TCR sequencing. We validated tessa and showed its superiority over existing approaches that investigate only the TCR sequences. With tessa, we demonstrated that TCR similarity constrains the phenotypes of T cells to be similar and dictates a gradient in antigen targeting efficiency of T cell clonotypes with convergent TCRs. We showed this constraint could predict a functional dichotomization of T cells postimmunotherapy treatment and is weakened in tumor contexts.

Original languageEnglish (US)
Pages (from-to)92-99
Number of pages8
JournalNature methods
Volume18
Issue number1
DOIs
StatePublished - Jan 2021

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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