Journal
NATURE BIOMEDICAL ENGINEERING
Volume 6, Issue 7, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41551-022-00874-6
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Funding
- Project for Cancer Research and Therapeutic Evolution (P-CREATE) from AMED [JP17cm0106417, JP20cm0106371]
- JSPS KAKENHI [18K19441, 16H06499, 16H06500, 21K18261, 21H02782, 21H02966]
- Practical Research for Innovative Cancer Control
- Grants-in-Aid for Scientific Research [21K18261, 21H02782, 21H02966, 16H06499, 18K19441, 16H06500] Funding Source: KAKEN
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By analyzing T cells at the single-cell level on a microwell array, researchers discovered that T-cell activation can occur via both trans and cis interactions, and successfully cloned tumor-antigen-specific TCRs.
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.
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