Agent-Based Modeling of T Cell Receptor Cooperativity.
Anastasios Siokis1, Philippe A Robert1, Michael Meyer-Hermann1,2
1Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, 38106 Braunschweig, Germany.
International Journal of Molecular Sciences
|September 9, 2020
Summary
This study models how T cell receptor (TCR) affinity changes during immune synapse formation. It suggests TCR-pMHC flow and F-actin feedback actively modulate affinity over time.
Area of Science:
- Immunology
- Computational Biology
- Biophysics
Background:
- Immune synapse (IS) formation is crucial for T cell antigen recognition.
- Evidence suggests T cell receptor (TCR) affinity is actively modulated during early signaling.
Purpose of the Study:
- To investigate potential mechanisms for TCR-antigen affinity modulation during IS formation using computational modeling.
- To explore the role of receptor density and molecular transport in affinity changes.
Main Methods:
- Agent-based modeling of TCR-pMHC interactions within the IS.
- Simulations comparing scenarios with and without centripetal transport (F-actin coupling).
- Incorporation of a mathematical model for F-actin foci feedback on association rates.
Main Results:
- Receptor-ligand affinity naturally evolves with ligand density and time without active mechanisms.
- Centripetal transport of TCR-pMHC complexes emerges as a potential affinity modulation mechanism.
- F-actin foci feedback on TCR-pMHC association rate (k_on) can actively tune TCR affinity.
Conclusions:
- The timing of affinity measurement is critical during IS development.
- TCR-pMHC complex dynamics and F-actin regulation are key factors in affinity modulation.
- Computational models provide insights into the active mechanisms governing TCR affinity during T cell activation.
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