ArticleProceedings of the National Academy of Sciences of the United States of America2017
Early T cell receptor signals globally modulate ligand:receptor affinities during antigen discrimination.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Liquid-liquid phase separation drives immune signaling transduction in cancer: a bibliometric and visualized study from 1992 to 2024.Frontiers in oncology · 2025Pooled it
- The spatial architecture of tumor immunity: Emerging predictive biomarkers across cancer.Immunologic research · 2026Review
- Actin waves guide an outward movement of microclusters in the lymphocyte immunological synapse.EMBO reports · 2026Article
- 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
- DNA Origami Tension Sensors (DOTS) for Single-Molecule Force Measurements at Fluid Intermembrane Junctions.Nano letters · 2025Article
- CD4+T-cells create a stable mechanical environment for force-sensitive TCR:pMHC interactions.Nature communications · 2025Article
- 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
- Morphodynamics of T-lymphocytes: Scanning to spreading.Biophysical journal · 2024Review
- Computational and experimental approaches to quantify protein binding interactions under confinement.Biophysical journal · 2024Review
- Rapid Optogenetic Clustering in the Cytoplasm with BcLOVclust.Journal of molecular biology · 2024Article
- Article
- Rapid optogenetic clustering of a cytoplasmic BcLOV4 variant.bioRxiv : the preprint server for biology · 2023Article
- cis-B7:CD28 interactions at invaginated synaptic membranes provide CD28 co-stimulation and promote CD8Immunity · 2023Article
- Micropatterning of functional lipid bilayer assays for quantitative bioanalysis.Biomicrofluidics · 2023Article
- Mechanical forces impair antigen discrimination by reducing differences in T-cell receptor/peptide-MHC off-rates.The EMBO journal · 2023Article
- DNA origami-based artificial antigen-presenting cells for adoptive T cell therapy.Science advances · 2022Article
- Discrete LAT condensates encode antigen information from single pMHC:TCR binding events.Nature communications · 2022Article
- Tuning T cell receptor sensitivity through catch bond engineering.Science (New York, N.Y.) · 2022Article
- T-cell Receptor Is a Threshold Detector: Sub- and Supra-Threshold Stochastic Resonance in TCR-MHC Clusters on the Cell Surface.Entropy (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Antigen discrimination by T cells occurs at the junction between a T cell and an antigen-presenting cell. Juxtacrine binding between numerous adhesion, signaling, and costimulatory molecules defines both the topographical and lateral geometry of this cell-cell interface, within which T cell receptor (TCR) and peptide major histocompatibility complex (pMHC) interact. These physical constraints on receptor and ligand movement have significant potential to modulate their molecular binding properties. Here, we monitor individual ligand:receptor binding and unbinding events in space and time by single-molecule imaging in live primary T cells for a range of different pMHC ligands and surface densities. Direct observations of pMHC:TCR and CD80:CD28 binding events reveal that the in situ affinity of both pMHC and CD80 ligands for their respective receptors is modulated by the steady-state number of agonist pMHC:TCR interactions experienced by the cell. By resolving every single pMHC:TCR interaction it is evident that this cooperativity is accomplished by increasing the kinetic on-rate without altering the off-rate and has a component that is not spatially localized. Furthermore, positive cooperativity is observed under conditions where the T cell activation probability is low. This TCR-mediated feedback is a global effect on the intercellular junction. It is triggered by the first few individual pMHC:TCR binding events and effectively increases the efficiency of TCR scanning for antigen before the T cell is committed to activation.
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