CD8+ T cells are critical to fight infections and to clear tumor cells. When they recognize their target cells, CD8+ T cells produce inflammatory cytokines and cytotoxic molecules. The production of these effector molecules must be well controlled: too little leads to the inability to control the pathogen, and too much can result in a life-threatening cytokine storm and tissue damage. A pivotal regulatory mechanism that defines the actual protein output in cells is post-transcriptional regulation (PTR). PTR determines the generation and the fate of messenger RNA, and the translation efficiency. RNA binding proteins (RBPs) are key modulators of these processes. However, to date the analysis of RBPs in modulating T cell effector function is anecdotal and focused on a few of the >2000 putative RBPs. A systematic analysis on RBP expression in T cells is to date lacking, yet key to define how PTR drives T cell effector function, and to define targets that help boost T cell responses against cancers.
Here, we have identified the RBP repertoire in primary human T cells. With state-of-the-art approaches we have determined how RBPs imprint the effector function of human CD8+ T cells. We have uncovered how RBP expression and interactions alter upon T cell activation, and we defined how these changes drive T cell responses. We have also revealed how RBPs can imprint and/or maintain the killer phenotype of human CD8+ T cells. Identifying these mechanisms should help to identify therapeutic targets to boost the cytotoxic potency of T cell products against e.g. cancers.
