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

V. Horkova, A. Drobek, D. Mueller, C. Gubser, V. Niederlova, L. Wyss, CG. King, D. Zehn, O. Stepanek

. 2020 ; 30 (5) : 1504-1514.e7. [pub] 20200204

Language English Country United States

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc21012869

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.

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$a Drobek, Ales $u Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences, 14220 Prague, Czech Republic
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$a Mueller, Daniel $u Department of Biomedicine, University Hospital and University of Basel, 4031 Basel, Switzerland
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$a Gubser, Celine $u Department of Biomedicine, University Hospital and University of Basel, 4031 Basel, Switzerland; Peter Doherty Institute, University of Melbourne, Melbourne, Australia
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$a Niederlova, Veronika $u Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences, 14220 Prague, Czech Republic
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