Time required for commitment to T cell proliferation depends on TCR affinity and cytokine response.
EMBO Rep
; 24(1): e54969, 2023 01 09.
Article
em En
| MEDLINE
| ID: mdl-36327141
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Citocinas
/
Linfócitos T CD8-Positivos
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article