Rapid cloning of antigen-specific T-cell receptors by leveraging the cis activation of T cells

Eiji Kobayashi, Aishun Jin, Hiroshi Hamana, Kiyomi Shitaoka, Kazuto Tajiri, Seisuke Kusano, Shigeyuki Yokoyama, Tatsuhiko Ozawa, Tsutomu Obata, Atsushi Muraguchi, Hiroyuki Kishi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

It is commonly understood that T cells are activated via trans interactions between antigen-specific T-cell receptors (TCRs) and antigenic peptides presented on major histocompatibility complex (MHC) molecules on antigen-presenting cells. By analysing a large number of T cells at the single-cell level on a microwell array, we show that T-cell activation can occur via cis interactions (where TCRs on the T cell interact with the antigenic peptides presented on MHC class-I molecules on the same cell), and that such cis activation can be used to detect antigen-specific T cells and clone their TCR within 4 d. We used the detection-and-cloning system to clone a tumour-antigen-specific TCR from peripheral blood mononuclear cells of healthy donors. TCR cloning by leveraging the cis activation of T cells may facilitate the development of TCR-engineered T cells for cancer therapy.

Original languageEnglish
Pages (from-to)806-818
Number of pages13
JournalNature Biomedical Engineering
Volume6
Issue number7
DOIs
StatePublished - 2022/07

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Computer Science Applications

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