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Updated: Oct 4, 2025
16:10
A TIRF Microscopy Technique for Real-time, Simultaneous Imaging of the TCR and its Associated Signaling Proteins
Published on: March 22, 2012
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Fluctuations in T cell receptor and pMHC interactions regulate T cell activation
Joseph R Egan1,2,3,4, Enas Abu-Shah4,5, Omer Dushek4
1Mathematical Sciences, Stem Cells and Regeneration, University of Southampton, Southampton SO17 1BJ, UK.
Journal of the Royal Society, Interface
|February 9, 2022
Summary
T cell activation relies on information from T cell receptor (TCR) and peptide major histocompatibility complex (pMHC) interactions, not just binding strength. Optimizing stochasticity in these dynamics could improve T cell therapies.
Area of Science:
- Immunology
- Computational Biology
- Biophysics
Background:
- Adaptive immune responses involve T cell receptor (TCR) and peptide major histocompatibility complex (pMHC) interactions.
- Low copy numbers of TCRs and pMHCs lead to stochastic interactions, with unclear effects on T cell function.
Purpose of the Study:
- To introduce a minimal stochastic model of T cell activation.
- To investigate the role of stochastic fluctuations in T cell function.
- To provide an information-theoretic interpretation of T cell activation.
Main Methods:
- Developed a minimal stochastic model incorporating serial TCR-pMHC engagement, reversible TCR conformational change, and TCR aggregation.
- Analyzed the model to determine factors eliciting immune responses.
Main Results:
- T cell activation is driven by information transfer (entropy rate of TCR-pMHC binding dynamics), not solely binding strength.
- The model explains various experimental observations regarding T cell activation.
Conclusions:
- T cell activation can be understood through an information-theoretic lens.
- Optimizing the stochasticity of TCR-pMHC binding dynamics may enhance T cell therapeutics.
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