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Cooperative stabilization of close-contact zones leads to sensitivity and selectivity in T-cell recognition

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Weikl,  Thomas R.
Thomas Weikl, Theorie & Bio-Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Citation

Różycki, B., & Weikl, T. R. (2021). Cooperative stabilization of close-contact zones leads to sensitivity and selectivity in T-cell recognition. Cells, 10(5): 1023. doi:10.3390/cells10051023.


Cite as: http://hdl.handle.net/21.11116/0000-0008-7D4D-7
Abstract
T cells are sensitive to 1 to 10 foreign-peptide-MHC complexes among a vast majority of self-peptide-MHC complexes, and discriminate selectively between peptide-MHC complexes that differ not much in their binding affinity to T-cell receptors (TCRs). Quantitative models that aim to explain this sensitivity and selectivity largely focus on single TCR/peptide-MHC complexes, but T cell adhesion involves a multitude of different complexes. In this article, we demonstrate in a three-dimensional computational model of T-cell adhesion that the cooperative stabilization of close-contact zones is sensitive to one to three foreign-peptide-MHC complexes and occurs at a rather sharp threshold affinity of these complexes, which implies selectivity. In these close-contact zones with lateral extensions of hundred to several hundred nanometers, few TCR/foreign-peptide-MHC complexes and many TCR/self-peptide-MHC complexes are segregated from LFA-1/ICAM-1 complexes that form at larger membrane separations. Previous high-resolution microscopy experiments indicate that the sensitivity and selectivity in the formation of closed-contact zones reported here are relevant for T-cell recognition, because the stabilization of close-contact zones by foreign, agonist peptide-MHC complexes precedes T-cell signaling and activation in the experiments.