Zfp36l1 establishes the high-affinity CD8 T-cell response by directly linking TCR affinity to cytokine sensing

Eur J Immunol. 2023 Dec 1:e2350700. doi: 10.1002/eji.202350700. Online ahead of print.ABSTRACTHow individual T cells compete for and respond to IL-2 at the molecular level, and, as a consequence, how this shapes population dynamics and the selection of high-affinity clones is still poorly understood. Here we describe how the RNA binding protein ZFP36L1, acts as a sensor of TCR affinity to promote clonal expansion of high-affinity CD8 T cells. As part of an incoherent feed-forward loop, ZFP36L1 has a nonredundant role in suppressing multiple negative regulators of cytokine signaling and mediating a selection mechanism based on competition for IL-2. We suggest that ZFP36L1 acts as a sensor of antigen affinity and establishes the dominance of high-affinity T cells by installing a hierarchical response to IL-2.PMID:38039407 | DOI:10.1002/eji.202350700

Source: European Journal of Immunology - December 1, 2023 Category: Allergy & Immunology Authors: Georg Petkau Twm J Mitchell Marian Jones Evans Louise Matheson Fiamma Salerno Martin Turner Source Type: research