ArticleCell reports2021
Allosteric activation of T cell antigen receptor signaling by quaternary structure relaxation.
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed.
- TCRζ-driven pre-signaling organization of Lck in Rab11⁺ endosomes shapes TCR activation.Cellular & molecular biology letters · 2026Article
- The resting and ligand-bound states of the membrane-embedded human T-cell receptor-CD3 complex.Nature communications · 2025Article
- TCR signal-enhancing mutation alters lipid metabolism of thymocytes and impairs antitumor immunity of mature T cells.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Solution structure and synaptic analyses reveal determinants of bispecific T cell engager potency.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The TCR and LCK: foundations for T-cell activation and therapeutic innovation.Frontiers in immunology · 2025Review
- The Evolving T Cell Receptor Recognition Code: The Rules Are More Like Guidelines.Immunological reviews · 2025Review
- In situ cell-surface conformation of the TCR-CD3 signaling complex.EMBO reports · 2024Article
- Mechanical force matters in early T cell activation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Cholesterol inhibits assembly and activation of the EphA2 receptor.bioRxiv : the preprint server for biology · 2024Article
- T-cell virtuosity in ''knowing thyself".Frontiers in immunology · 2024Review
- A Story of Kinases and Adaptors: The Role of Lck, ZAP-70 and LAT in Switch Panel Governing T-Cell Development and Activation.Biology · 2023Review
- Decoding the crosstalk between mevalonate metabolism and T cell function.Immunological reviews · 2023Review
- The Energetic Landscape of Catch Bonds in TCR Interfaces.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- Self-programmed dynamics of T cell receptor condensation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Recent advances in understanding TCR signaling: a synaptic perspective.Faculty reviews · 2023Review
- T-cell repertoire diversity: friend or foe for protective antitumor response?Journal of experimental & clinical cancer research : CR · 2022Review
- Molecular dynamics simulations reveal membrane lipid interactions of the full-length lymphocyte specific kinase (Lck).Scientific reports · 2022Article
- T cell and B cell antigen receptors share a conserved core transmembrane structure.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- Regulating the discriminatory response to antigen by T-cell receptor.Bioscience reports · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
16 authors.
Funding
Abstract
The mechanism of T cell antigen receptor (TCR-CD3) signaling remains elusive. Here, we identify mutations in the transmembrane region of TCRβ or CD3ζ that augment peptide T cell antigen receptor (pMHC)-induced signaling not explicable by enhanced ligand binding, lateral diffusion, clustering, or co-receptor function. Using a biochemical assay and molecular dynamics simulation, we demonstrate that the gain-of-function mutations loosen the interaction between TCRαβ and CD3ζ. Similar to the activating mutations, pMHC binding reduces TCRαβ cohesion with CD3ζ. This event occurs prior to CD3ζ phosphorylation and at 0°C. Moreover, we demonstrate that soluble monovalent pMHC alone induces signaling and reduces TCRαβ cohesion with CD3ζ in membrane-bound or solubilised TCR-CD3. Our data provide compelling evidence that pMHC binding suffices to activate allosteric changes propagating from TCRαβ to the CD3 subunits, reconfiguring interchain transmembrane region interactions. These dynamic modifications could change the arrangement of TCR-CD3 boundary lipids to license CD3ζ phosphorylation and initiate signal propagation.
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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.