Protein Kinase 2 (CK2) Controls CD8+ T-cell Effector and Memory Function during Infection

Protein kinase 2 (CK2) is a serine/threonine kinase composed of two catalytic subunits (CK2a and/or CK2a') and two regulatory subunits (CK2ß). CK2 has been shown to promote cancer progression by regulating the NF-?B, PI3K/AKT/mTOR, JAK/STAT and HIF-1a pathways, and also plays a critical role for immune cell development and function. However, the potential involvement of CK2 in CD8+ T-cell function has not explored. Here, we demonstrate that CK2 protein levels and kinase activity are enhanced upon CD8+ T-cell activation. CK2a deficiency results in impaired CD8+ T-cell activation and proliferation upon TCR stimulation. Furthermore, CK2a is involved in CD8+ T-cell metabolic reprogramming during activation through regulating the AKT/mTOR signaling pathway. Lastly, using a Listeria monocytogenes infection model, we demonstrate that CK2a is required for CD8+ T-cell expansion, maintenance and effector function in both primary and memory immune responses. Taken together, our study implicates CK2? as an important regulator of CD8+ T-cell activation and differentiation both in vitro and in vivo. Overall design: OT-I CK2afl/fl and OT-I CK2a-/- CD8+ T-cells were sorted from the spleen at day 7 post infection. Total RNA was extracted from FACS-sorted CD8+ T-cells using the miRNeasy Mini Kit (Qiagen, Venlo, Netherlands) according to the manufacturer's protocols and submitted to GENEWIZ (South Plainfield, NJ) for RNA sequencing (RNA-seq) and bioinformatics analysis.