ArticleImmunity2015
A Mechanical Switch Couples T Cell Receptor Triggering to the Cytoplasmic Juxtamembrane Regions of CD3ζζ.
Article in Immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed.
- Membrane-Based Assembly and Interactions in Immune Receptors.Chemical reviews · 2026Review
- Mechanical communication and function regulation of immune cells.Fundamental research · 2026Review
- The resting and ligand-bound states of the membrane-embedded human T-cell receptor-CD3 complex.Nature communications · 2025Article
- Mechanoregulation of lymphocyte cytotoxicity.Nature reviews. Immunology · 2025Review
- CAR T-cell therapy in hematologic and solid malignancies: mechanisms, clinical applications, and future directions.Medical oncology (Northwood, London, England) · 2025Review
- Review
- From TCR fundamental research to innovative chimeric antigen receptor design.Nature reviews. Immunology · 2025Review
- The TCR and LCK: foundations for T-cell activation and therapeutic innovation.Frontiers in immunology · 2025Review
- In situ cell-surface conformation of the TCR-CD3 signaling complex.EMBO reports · 2024Article
- Quantifying T cell receptor mechanics at membrane junctions using DNA origami tension sensors.Nature nanotechnology · 2024Article
- Focusing on CD8Journal of experimental & clinical cancer research : CR · 2024Review
- The effects of matrix stiffness on immune cells in bone biology.Mechanobiology in medicine · 2024Review
- Structures of human γδ T cell receptor-CD3 complex.Nature · 2024Article
- Article
- T-cell virtuosity in ''knowing thyself".Frontiers in immunology · 2024Review
- Phospho-mimetic CD3ε variants prevent TCR and CAR signaling.Frontiers in immunology · 2024Article
- The CD4 transmembrane GGXXG and juxtamembrane (C/F)CV+C motifs mediate pMHCII-specific signaling independently of CD4-LCK interactions.bioRxiv : the preprint server for biology · 2023Article
- Article
- Who wins the combat, CAR or TCR?Leukemia · 2023Review
- Apoptotic contraction drives target cell release by cytotoxic T cells.Nature immunology · 2023Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
The eight-subunit T cell receptor (TCR)-CD3 complex is the primary determinant for T cell fate decisions. Yet how it relays ligand-specific information across the cell membrane for conversion to chemical signals remains unresolved. We hypothesized that TCR engagement triggers a change in the spatial relationship between the associated CD3ζζ subunits at the junction where they emerge from the membrane into the cytoplasm. Using three in situ proximity assays based on ID-PRIME, FRET, and EPOR activity, we determined that the cytosolic juxtamembrane regions of the CD3ζζ subunits are spread apart upon assembly into the TCR-CD3 complex. TCR engagement then triggered their apposition. This mechanical switch resides upstream of the CD3ζζ intracellular motifs that initiate chemical signaling, as well as the polybasic stretches that regulate signal potentiation. These findings provide a framework from which to examine triggering events for activating immune receptors and other complex molecular machines.
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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 OpenQuestion graph.