Dynamics of the Coreceptor-LCK Interactions during T Cell Development Shape the Self-Reactivity of Peripheral CD4 and CD8 T Cells

Horková, Veronika; Drobek, Aleš; Mueller, D.; Gubser, C.; Niederlová, Veronika; Wyss, L.; King, C. G.; Zehn, D.; Štěpánek, Ondřej

doi:https://dx.doi.org/10.1016/j.celrep.2020.01.008

Number of the records: 1

Dynamics of the Coreceptor-LCK Interactions during T Cell Development Shape the Self-Reactivity of Peripheral CD4 and CD8 T Cells

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SYSNO ASEP	0524261
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Dynamics of the Coreceptor-LCK Interactions during T Cell Development Shape the Self-Reactivity of Peripheral CD4 and CD8 T Cells
Author(s)	Horková, Veronika (UMG-J)_ORCID Drobek, Aleš (UMG-J)_ORCID Mueller, D. (CH) Gubser, C. (CH) Niederlová, Veronika (UMG-J)_ORCID Wyss, L. (CH) King, C. G. (CH) Zehn, D. (DE) Štěpánek, Ondřej (UMG-J)_{RID, ORCID}
Number of authors	9
Source Title	Cell Reports. - : Cell Press - ISSN 2211-1247 Roč. 30, č. 5 (2020), s. 1504-1514
Number of pages	11 s.
Publication form	Online - E
Language	eng - English
Country	US - United States
Keywords	positive selection ; thymocyte development ; signal strength ; receptor ; affinity ; sensitivity ; antigens ; peptide ; binding ; themis
Subject RIV	EB - Genetics ; Molecular Biology
OECD category	Immunology
Subject RIV - cooperation	Genetics ; Molecular Biology
R&D Projects	GJ19-03435Y GA ČR - Czech Science Foundation (CSF)
	LM2015040 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	LO1419 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	LM2015062 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	ED2.1.00/19.0395 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
Method of publishing	Open access
Institutional support	UMG-J - RVO:68378050
UT WOS	000511294400019
DOI	10.1016/j.celrep.2020.01.008
Annotation	Overtly self-reactive T cells are removed during thymic selection. However, it has been recently established that T cell self-reactivity promotes protective immune responses. Apparently, the level of self-reactivity of mature T cells must be tightly balanced. Our mathematical model and experimental data show that the dynamic regulation of CD4- and CD8-LCK coupling establish the self-reactivity of the peripheral T cell pool. The stoichiometry of the interaction between CD8 and LCK, but not between CD4 and LCK, substantially increases upon T cell maturation. As a result, peripheral CD8(+) T cells are more self-reactive than CD4(+) T cells. The different levels of self-reactivity of mature CD8(+) and CD4(+) T cells likely reflect the unique roles of these subsets in immunity. These results indicate that the evolutionary selection pressure tuned the CD4-LCK and CD8-LCK stoichiometries, as they represent the unique parts of the proximal T cell receptor (TCR) signaling pathway, which differ between CD4(+) and CD8(+) T cells.
Workplace	Institute of Molecular Genetics
Contact	Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217
Year of Publishing	2021
Electronic address	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003063/

Number of the records: 1