ArticleFrontiers in immunology2013
Cellular-level versus receptor-level response threshold hierarchies in T-cell activation.
Article in Frontiers in immunology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- 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
- Dephosphorylation accelerates the dissociation of ZAP70 from the T cell receptor.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Staggered starts in the race to T cell activation.Trends in immunology · 2021Review
- CD8 coreceptor-mediated focusing can reorder the agonist hierarchy of peptide ligands recognized via the T cell receptor.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Human CD8Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Specificity of bispecific T cell receptors and antibodies targeting peptide-HLA.The Journal of clinical investigation · 2020Article
- Predicting Cross-Reactivity and Antigen Specificity of T Cell Receptors.Frontiers in immunology · 2020Review
- The expanding role of systems immunology in decoding the T cell receptor repertoire.Current opinion in systems biology · 2018Article
- Peptide mimic for influenza vaccination using nonnatural combinatorial chemistry.The Journal of clinical investigation · 2018Article
- Desensitized chimeric antigen receptor T cells selectively recognize target cells with enhanced antigen expression.Nature communications · 2018Article
- Structural Mechanism Underpinning Cross-reactivity of a CD8+ T-cell Clone That Recognizes a Peptide Derived from Human Telomerase Reverse Transcriptase.The Journal of biological chemistry · 2017Article
- Shared and Distinct Phenotypes and Functions of Human CD161++ Vα7.2+ T Cell Subsets.Frontiers in immunology · 2017Article
- Functional role of T-cell receptor nanoclusters in signal initiation and antigen discrimination.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- T cell receptor binding affinity governs the functional profile of cancer-specific CD8+ T cells.Clinical and experimental immunology · 2015Article
- Phenotypic models of T cell activation.Nature reviews. Immunology · 2014Review
- Bench, bedside, toolbox: T-cells deliver on every level.Frontiers in immunology · 2014Article
- Co-Receptor CD8-Mediated Modulation of T-Cell Receptor Functional Sensitivity and Epitope Recognition Degeneracy.Frontiers in immunology · 2013Review
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Peptide-MHC (pMHC) ligand engagement by T-cell receptors (TCRs) elicits a variety of cellular responses, some of which require substantially more TCR-mediated stimulation than others. This threshold hierarchy could reside at the receptor level, where different response pathways branch off at different stages of the TCR/CD3 triggering cascade, or at the cellular level, where the cumulative TCR signal registered by the T-cell is compared to different threshold values. Alternatively, dual-level thresholds could exist. In this study, we show that the cellular hypothesis provides the most parsimonious explanation consistent with data obtained from an in-depth analysis of distinct functional responses elicited in a clonal T-cell system by a spectrum of biophysically defined altered peptide ligands across a range of concentrations. Further, we derive a mathematical model that describes how ligand density, affinity, and off-rate all affect signaling in distinct ways. However, under the kinetic regime prevailing in the experiments reported here, the TCR/pMHC class I (pMHCI) dissociation rate was found to be the main governing factor. The CD8 coreceptor modulated the TCR/pMHCI interaction and altered peptide ligand potency. Collectively, these findings elucidate the relationship between TCR/pMHCI kinetics and cellular function, thereby providing an integrated mechanistic understanding of T-cell response profiles.
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