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

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

来源：Nature Biomedical Engineering, 2022, 6(7).

DOI：10.1038/s41551-022-00874-6

• IMMUNOLOGICAL SYNAPSE
• STRUCTURAL BASIS
• SELF-PEPTIDE
• CD8+T CELLS
• ALPHA-BETA
• MHC
• LYMPHOCYTES
• AFFINITY
• CANCER
• EFFICIENT

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 4d. 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.

• 单位
  哈尔滨医科大学