In the immune system, T cells can quickly discriminate between foreign and self ligands with high accuracy. There is significant evidence T-cells achieve this remarkable performance utilizing a network architecture based on  kinetic proofreading (KPR). KPR-based mechanisms actively consume energy to increase the specificity beyond what is possible in equilibrium.An important theoretical question that arises is to understand the trade-offs and fundamental limits on accuracy, speed, and dissipation (energy consumption) . Recent theoretical work suggests that it should always be possible to reduce the error of KPR-based mechanisms by waiting longer and /or consuming more energy. Surprisingly, we find that this is not the case and that there actually exists an optimal point in the speed-energy-accuracy plane for KPR and its generalizations . We give general arguments for why we expect this optimal to be a generic property of all KPR-based biochemical networks and discuss implications for our understanding of the T cell receptor circuit.
In the immune system, T cells can quickly discriminate between foreign and self ligands with high accuracy. There is evidence that T-cells achieve this remarkable performance utilizing a network architecture based on a generalization of kinetic proofreading (KPR). KPR-based mechanisms actively consume energy to increase the specificity beyond what is possible in equilibrium.An important theoretical question that arises is to understand the trade-offs and fundamental limits on accuracy, speed, and dissipation (energy consumption) in KPR and its generalization. Here, we revisit this question through numerical simulations where we simultaneously measure the speed, accuracy, and energy consumption of the KPR and adaptive sorting networks for different parameter choices. Our simulations highlight the existence of a 'feasible operating regime' in the speed-energy-accuracy plane where T-cells can quickly differentiate between foreign and self ligands at reasonable energy expenditure . We give general arguments for why we expect this feasible operating regime to be a generic property of all KPR-based biochemical networks and discuss implications for our understanding of the T cell receptor circuit.
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significant evidence
evidence that
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a generalization of
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. Recent theoretical work suggests that it should always be possible to reduce the error of KPR-based mechanisms by waiting longer and /or consuming more energy. Surprisingly, we find that this is not the case and that there actually exists an optimal point
in KPR and its generalization. Here, we revisit this question through numerical simulations where we simultaneously measure the speed, accuracy, and energy consumption of the KPR and adaptive sorting networks for different parameter choices. Our simulations highlight the existence of a 'feasible operating regime'
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for KPR and its generalizations
where T-cells can quickly differentiate between foreign and self ligands at reasonable energy expenditure
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optimal
feasible operating regime