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

Eiji KobayashiAi-Shun JinHiroshi HamanaKiyomi ShitaokaKazuto TajiriSeisuke KusanoShigeyuki YokoyamaTatsuhiko OzawaTsutomu ObataAtsushi MuraguchiHiroyuki Kishi
Published in: Nature biomedical engineering (2022)
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.
Keyphrases
  • single cell
  • regulatory t cells
  • cancer therapy
  • induced apoptosis
  • rna seq
  • drug delivery
  • high resolution
  • immune response
  • oxidative stress
  • stem cells
  • mesenchymal stem cells