ArticleProceedings of the National Academy of Sciences of the United States of America2010
Fast on-rates allow short dwell time ligands to activate T cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed.
- IFN-γ-producing self-reactive CD4+ T cells induce autoimmune adrenalitis in a mouse model of Addison's disease.JCI insight · 2026Article
- Mechanotransduction through T cell receptors: consensus, controversies and future outlooks.Experimental & molecular medicine · 2026Review
- Dynamical network analysis reveals long-range residue couplings at the pMHC interface underlying enhanced immunogenicity.NPJ systems biology and applications · 2026Article
- Murine T-cell receptor OT-I exhibits imperfect discrimination between foreign and self-antigens.The EMBO journal · 2026Article
- 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
- Advanced Quantification of Receptor-Ligand Interaction Lifetimes via Single-Molecule FRET Microscopy.Biomolecules · 2024Article
- Mechanical control of antigen detection and discrimination by T and B cell receptors.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
- Force-Induced Site-Specific Enzymatic Cleavage Probes Reveal That Serial Mechanical Engagement Boosts T Cell Activation.Journal of the American Chemical Society · 2024Article
- T-cell virtuosity in ''knowing thyself".Frontiers in immunology · 2024Review
- Mathematical models of TCR initial triggering.Frontiers in immunology · 2024Review
- Biochemical and biophysical characterization of natural polyreactivity in antibodies.Cell reports · 2023Article
- 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
- CD4Nature immunology · 2023Review
- Mechanical forces impair antigen discrimination by reducing differences in T-cell receptor/peptide-MHC off-rates.The EMBO journal · 2023Article
- I-ANature immunology · 2023Article
- The Enigmatic Nature of the TCR-pMHC Interaction: Implications for CAR-T and TCR-T Engineering.International journal of molecular sciences · 2022Review
- T cell microvilli simulations show operation near packing limit and impact on antigen recognition.Biophysical journal · 2022Article
- Covalent TCR-peptide-MHC interactions induce T cell activation and redirect T cell fate in the thymus.Nature communications · 2022Article
- Fluctuations in T cell receptor and pMHC interactions regulate T cell activation.Journal of the Royal Society, Interface · 2022Article
33 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors.
Funding
Abstract
Two contrasting theories have emerged that attempt to describe T-cell ligand potency, one based on the t(1/2) of the interaction and the other based on the equilibrium affinity (K(D)). Here, we have identified and studied an extensive set of T-cell receptor (TCR)-peptide-MHC (pMHC) interactions for CD4(+) cells that have differential K(D)s and kinetics of binding. Our data indicate that ligands with a short t(1/2) can be highly stimulatory if they have fast on-rates. Simple models suggest these fast kinetic ligands are stimulatory because the pMHCs bind and rebind the same TCR several times. Rebinding occurs when the TCR-pMHC on-rate outcompetes TCR-pMHC diffusion within the cell membrane, creating an aggregate t(1/2) (t(a)) that can be significantly longer than a single TCR-pMHC encounter. Accounting for t(a), ligand potency is K(D)-based when ligands have fast on-rates (k(on)) and t(1/2)-dependent when they have slow k(on). Thus, TCR-pMHC k(on) allow high-affinity short t(1/2) ligands to follow a kinetic proofreading model.
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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.