ArticleProceedings of the National Academy of Sciences of the United States of America2021
Trapping or slowing the diffusion of T cell receptors at close contacts initiates T cell signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Cell surface remodeling caused by the loss of the flippase subunit TMEM30A in immune cells.Journal of cell science · 2026Article
- Nanoscale protein clustering modulates the input-output response of cellular signalling pathways.Scientific reports · 2026Article
- Close Contacts Unlocked: Nanopore-Stabilized Microvilli Bypass T Cell Receptor-Ligand-Dependent T Cell Activation.ACS nano · 2026Article
- Remote Force Modulation of the T-Cell Receptor Reveals an NFAT-Threshold for CD4European journal of immunology · 2025Article
- The Structural Biology of T-Cell Antigen Detection at Close Contacts.Immunological reviews · 2025Review
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- Should Artificial Intelligence Play a Durable Role in Biomedical Research and Practice?International journal of molecular sciences · 2024Review
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- Ligand requirements for immunoreceptor triggering.Communications biology · 2024Article
- Antibody agonists trigger immune receptor signaling through local exclusion of receptor-type protein tyrosine phosphatases.Immunity · 2024Article
- Computational simulations of bispecific T cell engagers by a multiscale model.Biophysical journal · 2024Article
- Using CombiCells, a platform for titration and combinatorial display of cell surface ligands, to study T-cell antigen sensitivity modulation by accessory receptors.The EMBO journal · 2024Article
- The Energetic Landscape of Catch Bonds in TCR Interfaces.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- Antigen discrimination by T cells relies on size-constrained microvillar contact.Nature communications · 2023Article
- Influence of the extracellular domain size on the dynamic behavior of membrane proteins.Biophysical journal · 2022Article
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- T cells use distinct topographical and membrane receptor scanning strategies that individually coalesce during receptor recognition.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Engineering the T cell receptor for fun and profit: Uncovering complex biology, interrogating the immune system, and targeting disease.Current opinion in structural biology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
T cell activation is initiated by T cell receptor (TCR) phosphorylation. This requires the local depletion of large receptor-type phosphatases from "close contacts" formed when T cells interact with surfaces presenting agonistic TCR ligands, but exactly how the ligands potentiate signaling is unclear. It has been proposed that TCR ligands could enhance receptor phosphorylation and signaling just by holding TCRs in phosphatase-depleted close contacts, but this has not been directly tested. We devised simple methods to move the TCR in and out of close contacts formed by T cells interacting with supported lipid bilayers (SLBs) and to slow the receptor's diffusion in the contacts, using a series of anti-CD3ε Fab- and ligand-based adducts of the receptor. TCRs engaging a Fab extended with the large extracellular region of CD45 were excluded from contacts and produced no signaling. Conversely, allowing the extended Fab to become tethered to the SLB trapped the TCR in the close contacts, leading to very strong signaling. Importantly, attaching untethered anti-CD3ε Fab or peptide/MHC ligands, each of which were largely inactive in solution but both of which reduced TCR diffusion in close contacts approximately fivefold, also initiated signaling during cell/SLB contact. Our findings indicate that holding TCRs in close contacts or simply slowing their diffusion in phosphatase-depleted regions of the cell surface suffices to initiate signaling, effects we could reproduce in single-particle stochastic simulations. Our study shows that the TCR is preconfigured for signaling in a way that allows it to be triggered by ligands acting simply as receptor "traps."
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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.