ArticleCell2014
Coreceptor scanning by the T cell receptor provides a mechanism for T cell tolerance.
Article in Cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
107 citing papers in PubMed, 164 citations in OpenAlex.
- Calibrating T cell responsiveness through interactions with self.Nature reviews. Immunology · 2026Review
- Mechanotransduction through T cell receptors: consensus, controversies and future outlooks.Experimental & molecular medicine · 2026Review
- Evaluating the effects of CD8/CD4 on T cell function in terms of TCR-pMHC-coreceptor catch and slip bonds.Frontiers in immunology · 2026Article
- Murine T-cell receptor OT-I exhibits imperfect discrimination between foreign and self-antigens.The EMBO journal · 2026Article
- Evaluating the effects of CD8/CD4 on T cell function in terms of TCR-pMHC-coreceptor catch and slip bonds.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
- TCR catch bonds nonlinearly control CD8 cooperation to shape T cell specificity.Cell research · 2025Article
- The TCR and LCK: foundations for T-cell activation and therapeutic innovation.Frontiers in immunology · 2025Review
- The partitioning of TCR repertoires by thymic selection.The Journal of experimental medicine · 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
- 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
- Structure, function, and immunomodulation of the CD8 co-receptor.Frontiers in immunology · 2024Review
- Mathematical models of TCR initial triggering.Frontiers in immunology · 2024Review
- OT-I TCR Transgenic Mice to Study the Role of PTPN22 in Anti-cancer Immunity.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Proofreading does not result in more reliable ligand discrimination in receptor signaling due to its inherent stochasticity.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Mechanical forces impair antigen discrimination by reducing differences in T-cell receptor/peptide-MHC off-rates.The EMBO journal · 2023Article
- A single-amino acid substitution in the adaptor LAT accelerates TCR proofreading kinetics and alters T-cell selection, maintenance and function.Nature immunology · 2023Article
- Article
- Time required for commitment to T cell proliferation depends on TCR affinity and cytokine response.EMBO reports · 2023Article
- The kinase occupancy of T cell coreceptors reconsidered.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
47 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
In the thymus, high-affinity, self-reactive thymocytes are eliminated from the pool of developing T cells, generating central tolerance. Here, we investigate how developing T cells measure self-antigen affinity. We show that very few CD4 or CD8 coreceptor molecules are coupled with the signal-initiating kinase, Lck. To initiate signaling, an antigen-engaged T cell receptor (TCR) scans multiple coreceptor molecules to find one that is coupled to Lck; this is the first and rate-limiting step in a kinetic proofreading chain of events that eventually leads to TCR triggering and negative selection. MHCII-restricted TCRs require a shorter antigen dwell time (0.2 s) to initiate negative selection compared to MHCI-restricted TCRs (0.9 s) because more CD4 coreceptors are Lck-loaded compared to CD8. We generated a model (Lck come&stay/signal duration) that accurately predicts the observed differences in antigen dwell-time thresholds used by MHCI- and MHCII-restricted thymocytes to initiate negative selection and generate self-tolerance.
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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 Socratic graph.