ArticleScience signaling2019
Mapping the stochastic sequence of individual ligand-receptor binding events to cellular activation: T cells act on the rare events.
Article in Science signaling, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- Liquid-liquid phase separation drives immune signaling transduction in cancer: a bibliometric and visualized study from 1992 to 2024.Frontiers in oncology · 2025Pooled it
- T cells are blind to the dark mechanics of tumors.Trends open · 2026Review
- Distinguishing near- versus off-critical phase behaviors of intrinsically disordered proteins.Reports on progress in physics. Physical Society (Great Britain) · 2026Article
- Disordered protein LAT encodes relative levels of signaling pathways in T cell activation.Science (New York, N.Y.) · 2026Article
- Subcellular glycan-mannose receptor binding kinetics correlate with myeloid cell function.Nature communications · 2025Article
- T cell costimulatory and inhibitory signals differentially modulate LAT condensate nucleation propensity after TCR ligation.bioRxiv : the preprint server for biology · 2025Article
- Parallel reactions on a single T cell receptor offer a robust kinetic proofreading mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- Somatic Mutations in DNA Mismatch Repair Genes, Mutation Rate and Neoantigen Load in Acute Lymphoblastic Leukemia.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Enzymatic Reactions Dictated by the 2D Membrane Environment.The journal of physical chemistry letters · 2025Article
- Proofreading and single-molecule sensitivity in T cell receptor signaling by condensate nucleation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- ATLAS-seq: a microfluidic single-cell TCR screen for antigen-reactive TCRs.Nature communications · 2025Article
- Should Artificial Intelligence Play a Durable Role in Biomedical Research and Practice?International journal of molecular sciences · 2024Review
- Differential roles of kinetic on- and off-rates in T-cell receptor signal integration revealed with a modified Fab'-DNA ligand.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Mechanical control of antigen detection and discrimination by T and B cell receptors.Biophysical journal · 2024Review
- Morphodynamics of T-lymphocytes: Scanning to spreading.Biophysical journal · 2024Review
- Differential Roles of Kinetic On- and Off-Rates in T-Cell Receptor Signal Integration Revealed with a Modified Fab'-DNA Ligand.bioRxiv : the preprint server for biology · 2024Article
- Antigen perception in T cells by long-term Erk and NFAT signaling dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Modulation of antigen discrimination by duration of immune contacts in a kinetic proofreading model of T cell activation with extreme statistics.PLoS computational biology · 2023Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
T cell receptor (TCR) binding to agonist peptide major histocompatibility complex (pMHC) triggers signaling events that initiate T cell responses. This system is remarkably sensitive, requiring only a few binding events to successfully activate a cellular response. On average, activating pMHC ligands exhibit mean dwell times of at least a few seconds when bound to the TCR. However, a T cell accumulates pMHC-TCR interactions as a stochastic series of discrete, single-molecule binding events whose individual dwell times are broadly distributed. With activation occurring in response to only a handful of such binding events, individual cells are unlikely to experience the average binding time. Here, we mapped the ensemble of pMHC-TCR binding events in space and time while simultaneously monitoring cellular activation. Our findings revealed that T cell activation hinges on rare, long-dwell time binding events that are an order of magnitude longer than the average agonist pMHC-TCR dwell time. Furthermore, we observed that short pMHC-TCR binding events that were spatially correlated and temporally sequential led to cellular activation. These observations indicate that T cell antigen discrimination likely occurs by sensing the tail end of the pMHC-TCR binding dwell time distribution rather than its average properties.
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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.