ArticleJournal of theoretical biology2008
Stochastic effects and bistability in T cell receptor signaling.
Article in Journal of theoretical biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 92 citations in OpenAlex.
- A comparative mathematical modeling study of phenotypic approaches to T cell activation.Scientific reports · 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
- Reliable ligand discrimination in stochastic multistep kinetic proofreading: First passage time vs. product counting strategies.PLoS computational biology · 2024Article
- Modelling the interplay between the CD4Journal of mathematical biology · 2021Article
- Autophosphorylation and the Dynamics of the Activation of Lck.Bulletin of mathematical biology · 2021Article
- How the T cell signaling network processes information to discriminate between self and agonist ligands.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Towards multiscale modeling of the CD8Wiley interdisciplinary reviews. Systems biology and medicine · 2019Review
- Scaling methods for accelerating kinetic Monte Carlo simulations of chemical reaction networks.The Journal of chemical physics · 2019Article
- Immunobiochemical Reconstruction of Influenza Lung Infection-Melanoma Skin Cancer Interactions.Frontiers in immunology · 2019Article
- Single-cell RNA sequencing to explore immune cell heterogeneity.Nature reviews. Immunology · 2018Review
- Mathematical modeling identifies Lck as a potential mediator for PD-1 induced inhibition of early TCR signaling.PloS one · 2018Article
- Untangling the Hairball: Fitness-Based Asymptotic Reduction of Biological Networks.Biophysical journal · 2017Article
- Contractile actomyosin arcs promote the activation of primary mouse T cells in a ligand-dependent manner.PloS one · 2017Article
- Mathematical Models for Immunology: Current State of the Art and Future Research Directions.Bulletin of mathematical biology · 2016Review
- Efficient Optimization of Stimuli for Model-Based Design of Experiments to Resolve Dynamical Uncertainty.PLoS computational biology · 2015Article
- Experimental and theoretical bases for mechanisms of antigen discrimination by T cells.Biophysics (Nagoya-shi, Japan) · 2015Review
- Modeling the T cell immune response: a fascinating challenge.Journal of pharmacokinetics and pharmacodynamics · 2014Review
- Phenotypic models of T cell activation.Nature reviews. Immunology · 2014Review
- Multiple model-informed open-loop control of uncertain intracellular signaling dynamics.PLoS computational biology · 2014Article
- Composing problem solvers for simulation experimentation: a case study on steady state estimation.PloS one · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
The stochastic dynamics of T cell receptor (TCR) signaling are studied using a mathematical model intended to capture kinetic proofreading (sensitivity to ligand-receptor binding kinetics) and negative and positive feedback regulation mediated, respectively, by the phosphatase SHP1 and the MAP kinase ERK. The model incorporates protein-protein interactions involved in initiating TCR-mediated cellular responses and reproduces several experimental observations about the behavior of TCR signaling, including robust responses to as few as a handful of ligands (agonist peptide-MHC complexes on an antigen-presenting cell), distinct responses to ligands that bind TCR with different lifetimes, and antagonism. Analysis of the model indicates that TCR signaling dynamics are marked by significant stochastic fluctuations and bistability, which is caused by the competition between the positive and negative feedbacks. Stochastic fluctuations are such that single-cell trajectories differ qualitatively from the trajectory predicted in the deterministic approximation of the dynamics. Because of bistability, the average of single-cell trajectories differs markedly from the deterministic trajectory. Bistability combined with stochastic fluctuations allows for switch-like responses to signals, which may aid T cells in making committed cell-fate decisions.
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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.