Dataset Information

Identifying feasible operating regimes for early T-cell recognition: The speed, energy, accuracy trade-off in kinetic proofreading and adaptive sorting.

ABSTRACT: 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.

SUBMITTER: Cui W

PROVIDER: S-EPMC6095552 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Identifying feasible operating regimes for early T-cell recognition: The speed, energy, accuracy trade-off in kinetic proofreading and adaptive sorting.

Cui Wenping W Mehta Pankaj P

PloS one 20180816 8

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, a ...[more]

PMID: 30114236

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Project description:The ability to dynamically and rapidly adjust task performance based on its outcome is fundamental to adaptive, flexible behavior. Over trials of a task, responses speed up until an error is committed and after the error responses slow down. These dynamic adjustments serve to optimize performance and are well-described by the speed-accuracy trade-off (SATO) function. We hypothesized that SATOs based on outcomes reflect reciprocal changes in the allocation of attention between the internal milieu and the task-at-hand, as indexed by reciprocal changes in activity between the default and dorsal attention brain networks. We tested this hypothesis using functional MRI to examine the pattern of network activation over a series of trials surrounding and including an error. We further hypothesized that these reciprocal changes in network activity are coordinated by the posterior cingulate cortex (PCC) and would rely on the structural integrity of its white matter connections. Using diffusion tensor imaging, we examined whether fractional anisotropy of the posterior cingulum bundle correlated with the magnitude of reciprocal changes in network activation around errors. As expected, reaction time (RT) in trials surrounding errors was consistent with predictions from the SATO function. Activation in the default network was: (i) inversely correlated with RT, (ii) greater on trials before than after an error and (iii) maximal at the error. In contrast, activation in the right intraparietal sulcus of the dorsal attention network was (i) positively correlated with RT and showed the opposite pattern: (ii) less activation before than after an error and (iii) the least activation on the error. Greater integrity of the posterior cingulum bundle was associated with greater reciprocity in network activation around errors. These findings suggest that dynamic changes in attention to the internal versus external milieu in response to errors underlie SATOs in RT and are mediated by the PCC.

Dataset Information

Identifying feasible operating regimes for early T-cell recognition: The speed, energy, accuracy trade-off in kinetic proofreading and adaptive sorting.

Publications

Identifying feasible operating regimes for early T-cell recognition: The speed, energy, accuracy trade-off in kinetic proofreading and adaptive sorting.

Similar Datasets

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