Author:
Chan Cliburn,George Andrew J. T.,Stark Jaroslav
Abstract
Two of the most important models to account for the specificity and
sensitivity of the T cell receptor (TCR) are the kinetic proofreading
and serial ligation models. However, although kinetic proofreading
provides a means for individual TCRs to measure accurately the length
of time they are engaged and signal appropriately, the stochastic
nature of ligand dissociation means the kinetic proofreading model
implies that at high concentrations the response of the cell will be
relatively nonspecific. Recent ligand experiments have revealed the
phenomenon of both negative and positive crosstalk among neighboring
TCRs. By using a Monte Carlo simulation of a lattice of TCRs, we
integrate receptor crosstalk with the kinetic proofreading and serial
ligation models and discover that receptor cooperativity can enhance T
cell specificity significantly at a very modest cost to the sensitivity
of the response.
Publisher
Proceedings of the National Academy of Sciences
Cited by
58 articles.
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