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

Abstract

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.