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

Veronika Horkova, Ales Drobek, Daniel Mueller, Celine Gubser, Veronika Niederlova, Lena Wyss, Carolyn G. King, Dietmar Zehn, Ondrej Stepanek*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

28 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1504-1514.e7
JournalCell Reports
Volume30
Issue number5
DOIs
Publication statusPublished - 4 Feb 2020
Externally publishedYes

Keywords

  • CD4
  • CD8
  • LCK
  • T cell
  • TCR
  • evolution of the immune system
  • lymphocyte
  • self-reactivity
  • signaling
  • thymus

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