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

0524261 - ÚMG 2021 RIV US eng J - Journal Article
Horková, Veronika - Drobek, Aleš - Mueller, D. - Gubser, C. - Niederlová, Veronika - Wyss, L. - King, C. G. - Zehn, D. - Štěpánek, Ondřej
Dynamics of the Coreceptor-LCK Interactions during T Cell Development Shape the Self-Reactivity of Peripheral CD4 and CD8 T Cells.
Cell Reports. Roč. 30, č. 5 (2020), s. 1504-1514. ISSN 2211-1247. E-ISSN 2211-1247
R&D Projects: GA ČR GJ19-03435Y; GA MŠMT(CZ) LM2015040; GA MŠMT LO1419; GA MŠMT(CZ) LM2015062; GA MŠMT ED2.1.00/19.0395
Institutional support: RVO:68378050
Keywords : positive selection * thymocyte development * signal strength * receptor * affinity * sensitivity * antigens * peptide * binding * themis
OECD category: Immunology
Impact factor: 9.423, year: 2020
Method of publishing: Open access
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003063/

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.
Permanent Link: http://hdl.handle.net/11104/0308645