ArticleBiophysical journal2006
Ligand detection and discrimination by spatial relocalization: A kinase-phosphatase segregation model of TCR activation.
Article in Biophysical journal, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 58 citations in OpenAlex.
- The Structural Biology of T-Cell Antigen Detection at Close Contacts.Immunological reviews · 2025Review
- Should Artificial Intelligence Play a Durable Role in Biomedical Research and Practice?International journal of molecular sciences · 2024Review
- Ligand requirements for immunoreceptor triggering.Communications biology · 2024Article
- Understanding How Cells Probe the World: A Preliminary Step towards Modeling Cell Behavior?International journal of molecular sciences · 2023Article
- Joining Forces for Cancer Treatment: From "TCR versus CAR" to "TCR and CAR".International journal of molecular sciences · 2022Review
- Regulation of T cell function by protein S-acylation.Frontiers in physiology · 2022Review
- Nanoscale Colocalization of NK Cell Activating and Inhibitory Receptors Controls Signal Integration.Frontiers in immunology · 2022Article
- Mechanotransduction as a major driver of cell behaviour: mechanisms, and relevance to cell organization and future research.Open biology · 2021Review
- Bispecific T Cell Engagers for the Treatment of Multiple Myeloma: Achievements and Challenges.Cancers · 2021Review
- Development of a Simple Kinetic Mathematical Model of Aggregation of Particles or Clustering of Receptors.Life (Basel, Switzerland) · 2020Article
- T Cell Membrane Heterogeneity Aids Antigen Recognition and T Cell Activation.Frontiers in cell and developmental biology · 2020Review
- TCR-pMHC kinetics under force in a cell-free system show no intrinsic catch bond, but a minimal encounter duration before binding.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- A cell topography-based mechanism for ligand discrimination by the T cell receptor.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Spatial control of Draper receptor signaling initiates apoptotic cell engulfment.The Journal of cell biology · 2018Article
- 2D Kinetic Analysis of TCR and CD8 Coreceptor for LCMV GP33 Epitopes.Frontiers in immunology · 2018Article
- Cytoskeletal actin dynamics shape a ramifying actin network underpinning immunological synapse formation.Science advances · 2017Article
- Mathematical Models for Immunology: Current State of the Art and Future Research Directions.Bulletin of mathematical biology · 2016Review
- Initiation of T cell signaling by CD45 segregation at 'close contacts'.Nature immunology · 2016Article
- Phenotypic models of T cell activation.Nature reviews. Immunology · 2014Review
- Regulation of T-cell receptor signaling by the actin cytoskeleton and poroelastic cytoplasm.Immunological reviews · 2013Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
We develop a model of tyrosine phosphorylation and activation of the T-cell receptor (TCR) by localization to regions of close membrane-membrane proximity (close contact) that physically exclude tyrosine phosphatases such as CD45. Phosphatase exclusion generates regions of low phosphatase and high kinase activity and thus our model provides a framework to examine the kinetic segregation model of TCR activation. We incorporate a sequence of activation steps modeling the construction of the signalosome with a final sequestered, or high-stability, signaling state. The residence time of unbound TCRs in tyrosine kinase-rich domains is shown to be too short for accumulation of activation steps, whereas binding to an agonist lengthens the localization time and leads to generation of fully active TCRs. Agonist detection depends only on this localization, and therefore kinetic segregation represents a viable ligand detection mechanism, or signal transduction mechanism across membranes, distinct from receptor oligomerization and conformational change. We examine the degree of discrimination of agonists from a background of null (self) peptides, and from weak agonists achievable by this mechanism.
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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.