ArticleThe EMBO journal2023
Mechanical forces impair antigen discrimination by reducing differences in T-cell receptor/peptide-MHC off-rates.
Article in The EMBO journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 51 citations in OpenAlex.
- T cells are blind to the dark mechanics of tumors.Trends open · 2026Review
- Generation of T cells with reduced off-target cross-reactivities by engineering co-signalling receptors.Nature biomedical engineering · 2026Article
- Mechanotransduction through T cell receptors: consensus, controversies and future outlooks.Experimental & molecular medicine · 2026Review
- Evaluating the effects of CD8/CD4 on T cell function in terms of TCR-pMHC-coreceptor catch and slip bonds.Frontiers in immunology · 2026Article
- Murine T-cell receptor OT-I exhibits imperfect discrimination between foreign and self-antigens.The EMBO journal · 2026Article
- Evaluating the effects of CD8/CD4 on T cell function in terms of TCR-pMHC-coreceptor catch and slip bonds.bioRxiv : the preprint server for biology · 2025Article
- Mechanoregulation of lymphocyte cytotoxicity.Nature reviews. Immunology · 2025Review
- CD4+T-cells create a stable mechanical environment for force-sensitive TCR:pMHC interactions.Nature communications · 2025Article
- Mechanical interactions impact the functions of immune cells and their application in immunoengineering.Advanced therapeutics · 2025Article
- Microdevice for confinement of T-cells on functionalized bio-interfaces.Lab on a chip · 2025Article
- Tumor cells escape immunosurveillance by hampering LFA-1.Frontiers in immunology · 2025Review
- The Evolving T Cell Receptor Recognition Code: The Rules Are More Like Guidelines.Immunological reviews · 2025Review
- Mechanical force matters in early T cell activation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Parsing digital or analog TCR performance through piconewton forces.Science advances · 2024Article
- Advanced Quantification of Receptor-Ligand Interaction Lifetimes via Single-Molecule FRET Microscopy.Biomolecules · 2024Article
- Morphodynamics of T-lymphocytes: Scanning to spreading.Biophysical journal · 2024Review
- The physical landscape of CAR-T synapse.Biophysical journal · 2024Review
- Mechanical control of antigen detection and discrimination by T and B cell receptors.Biophysical journal · 2024Review
- Mechanical regulation of lymphocyte activation and function.Journal of cell science · 2024Review
- A Microfluidic Strategy to Capture Antigen-Specific High-Affinity B Cells.Advanced nanobiomed research · 2024Article
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Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
Abstract
T cells use their T-cell receptors (TCRs) to discriminate between lower-affinity self and higher-affinity foreign peptide major-histocompatibility-complexes (pMHCs) based on the TCR/pMHC off-rate. It is now appreciated that T cells generate mechanical forces during this process but how force impacts the TCR/pMHC off-rate remains debated. Here, we measured the effect of mechanical force on the off-rate of multiple TCR/pMHC interactions. Unexpectedly, we found that lower-affinity TCR/pMHCs with faster solution off-rates were more resistant to mechanical force (weak slip or catch bonds) than higher-affinity interactions (strong slip bonds). This was confirmed by molecular dynamics simulations. Consistent with these findings, we show that the best-characterized catch bond, involving the OT-I TCR, has a low affinity and an exceptionally fast solution off-rate. Our findings imply that reducing forces on the TCR/pMHC interaction improves antigen discrimination, and we suggest a role for the adhesion receptors CD2 and LFA-1 in force-shielding the TCR/pMHC interaction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.