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

Petkau, G.; Mitchell, T.; Jones Evans, M.; Matheson, L. S.; Salerno, F.; Turner, M.

doi:10.1101/2023.05.11.539978

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bioRxiv · 10.1101/2023.05.11.539978

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

Petkau, G.·Mitchell, T.·Jones Evans, M.·Matheson, L. S.·Salerno, F.·Turner, M.

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Abstract

How individual T cells compete for and respond to IL2 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 non-redundant role in suppressing negative regulators of cytokine signalling and mediating a selection mechanism based on competition for IL2. We suggest that ZFP36L1 acts as a sensor of antigen affinity and establishes dominance of high affinity T cells by installing a hierarchical response to IL2.

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Petkau, G., Mitchell, T., Jones Evans, M., Matheson, L. S., Salerno, F., Turner, M.. 2023-05-13. Zfp36l1 establishes the high affinity CD8 T cell response by directly linking TCR affinity to cytokine sensing. https://doi.org/10.1101/2023.05.11.539978

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