ArticleeLife2019
Optogenetic control shows that kinetic proofreading regulates the activity of the T cell receptor.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed.
- Multicolor and Attenuated Light Intensity Responses in Protein Hydrogels Arising from Photoregulated Crosslink Dynamics.Angewandte Chemie (International ed. in English) · 2026Article
- Graph neural network modeling of receptor interaction kinetics from single-molecule imaging data.bioRxiv : the preprint server for biology · 2026Article
- Potassium suppresses allosteric activation of ZAP-70-dependent T cell receptor signaling.The Journal of biological chemistry · 2026Article
- Lights up on the embryonic dance: tools and applications of optogenetics in developmental biology.Genes & development · 2026Review
- Mechanotransduction through T cell receptors: consensus, controversies and future outlooks.Experimental & molecular medicine · 2026Review
- T cell decision-making decodes the dynamic antigenic landscape.Frontiers in immunology · 2026Review
- Coupling Recombinant PhyB to Cell Culture Plates and Beads.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Opto-APCs: Displaying Phytochrome B on the Surface of Living Cells for Optogenetic Studies.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
- Mechanisms of T cell activation: Integrating signaling pathways, experimental models, and therapeutic implications.EXCLI journal · 2026Review
- 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
- Optogenetic engineering for precision cancer immunotherapy.Trends in pharmacological sciences · 2025Review
- Optogenetic control of T cells for immunomodulation.Essays in biochemistry · 2025Review
- 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
- Multiscale Responsive Kinetic Modeling: Quantifying Biomolecular Reaction Flux under Varying Electrochemical Conditions.Journal of chemical theory and computation · 2025Article
- Opto-CD28-REACT: optogenetic co-stimulatory receptor activation on non-engineered human T cells.Frontiers in immunology · 2025Article
- The TCR and LCK: foundations for T-cell activation and therapeutic innovation.Frontiers in immunology · 2025Review
- Genetically-stable engineered optogenetic gene switches modulate spatial cell morphogenesis in two- and three-dimensional tissue cultures.Nature communications · 2024Article
- Physical extraction of antigen and information.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Plant Phytochrome Interactions Decode Light and Temperature Signals.The Plant cell · 2024Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
The immune system distinguishes between self and foreign antigens. The kinetic proofreading (KPR) model proposes that T cells discriminate self from foreign ligands by the different ligand binding half-lives to the T cell receptor (TCR). It is challenging to test KPR as the available experimental systems fall short of only altering the binding half-lives and keeping other parameters of the interaction unchanged. We engineered an optogenetic system using the plant photoreceptor phytochrome B (PhyB) as a ligand to selectively control the dynamics of ligand binding to the TCR by light. This opto-ligand-TCR system was combined with the unique property of PhyB to continuously cycle between the binding and non-binding states under red light, with the light intensity determining the cycling rate and thus the binding duration. Mathematical modeling of our experimental datasets showed that indeed the ligand-TCR interaction half-life is the decisive factor for activating downstream TCR signaling, substantiating KPR.
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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.