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Time required for commitment to T cell proliferation depends on TCR affinity and cytokine response.

Liang-Zhe WuRenu BalyanJoanna BrzostekXiang ZhaoNicholas R J Gascoigne
Published in: EMBO reports (2022)
T cell activation and effector functions are determined by the affinity of the interaction between T cell receptor (TCR) and its antigenic peptide MHC (pMHC) ligand. A better understanding of the quantitative aspects of TCR-pMHC affinity-dependent T cell activation is critical for the development of new immunotherapeutic strategies. However, the role of TCR-pMHC affinity in regulating the kinetics of CD8 + T cell commitment to proliferation and differentiation is unknown. Here, we show that the stronger the TCR-pMHC affinity, the shorter the time of T cell-APC co-culture required to commit CD8 + T cells to proliferation. The time threshold for T cell cytokine production is much lower than that for cell proliferation. There is a strong correlation between affinity-dependent differences in AKT phosphorylation and T cell proliferation. The cytokine IL-15 increases the poor proliferation of T cells stimulated with low affinity pMHC, suggesting that pro-inflammatory cytokines can override the affinity-dependent features of T cell proliferation.
Keyphrases
  • cell proliferation
  • regulatory t cells
  • signaling pathway
  • capillary electrophoresis
  • cell cycle
  • anti inflammatory