ArticleeLife2019
Light-based tuning of ligand half-life supports kinetic proofreading model of T cell signaling.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed.
- LAT condensation gates PLCγ1 activation via bimodal LAT phosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The geometry of pMHC-coated nanoparticles and T-cell receptor clusters governs the sensitivity-specificity trade-off in T-cell response: a modeling investigation.Immunology and cell biology · 2026Article
- T Cell Receptor Co-Stimulation Through Magnetogenetic Tools: A Platform for Wireless Rewiring of Cellular Signaling.ACS omega · 2026Article
- Coupling Recombinant PhyB to Cell Culture Plates and Beads.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Murine T-cell receptor OT-I exhibits imperfect discrimination between foreign and self-antigens.The EMBO journal · 2026Article
- 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
- 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
- Remote Force Modulation of the T-Cell Receptor Reveals an NFAT-Threshold for CD4European journal of immunology · 2025Article
- The current landscape of optogenetics for the enhancement of adoptive T-cell therapy.Discovery immunology · 2025Review
- Optogenetic Clustering and Stimulation of the T Cell Receptor in Nongenetically Modified Human T Cells.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Opto-CD28-REACT: optogenetic co-stimulatory receptor activation on non-engineered human T cells.Frontiers in immunology · 2025Article
- Flotillin-2 dampens T cell antigen sensitivity and functionality.JCI insight · 2024Article
- Flotillin-2 dampens T cell antigen sensitivity and functionality.JCI insight · 2024Article
- Article
- Reliable ligand discrimination in stochastic multistep kinetic proofreading: First passage time vs. product counting strategies.PLoS computational 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
- 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
- Membrane-proximal motifs encode differences in signaling strength between type I and III interferon receptors.Science signaling · 2023Article
- Light-inducible T cell engagers trigger, tune, and shape the activation of primary T cells.Proceedings of the National Academy of Sciences of the United States of America · 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
1 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors.
Funding
Abstract
T cells are thought to discriminate self from foreign peptides by converting small differences in ligand binding half-life into large changes in cell signaling. Such a kinetic proofreading model has been difficult to test directly, as existing methods of altering ligand binding half-life also change other potentially important biophysical parameters, most notably the mechanical stability of the receptor-ligand interaction. Here we develop an optogenetic approach to specifically tune the binding half-life of a chimeric antigen receptor without changing other binding parameters and provide direct evidence of kinetic proofreading in T cell signaling. This half-life discrimination is executed in the proximal signaling pathway, downstream of ZAP70 recruitment and upstream of diacylglycerol accumulation. Our methods represent a general tool for temporal and spatial control of T cell signaling and extend the reach of optogenetics to probe pathways where the individual molecular kinetics, rather than the ensemble average, gates downstream signaling.
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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.