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

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.

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Różycki, Bartosz, Author
Weikl, Thomas R.1, Author              
Affiliations:
1Thomas Weikl, Theorie & Bio-Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863330              

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Free keywords: T-cell receptor; adhesion-induced segregation; microcluster; membrane bending; modeling and simulation
 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.

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Language(s): eng - English
 Dates: 2021-04-262021
 Publication Status: Published in print
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 Rev. Type: -
 Identifiers: DOI: 10.3390/cells10051023
DOI: doi.org/10.1101/2021.03.02.433515
BibTex Citekey: cells10051023
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Title: Cells
Source Genre: Journal
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Publ. Info: Basel, Switzerland : MDPI
Pages: - Volume / Issue: 10 (5) Sequence Number: 1023 Start / End Page: - Identifier: ISSN: 2073-4409