Eight diverse isoforms of Protein Kinases C (PKCs) are expressed in T lymphocytes. They regulate numerous cellular processes (cell activation, proliferation, migration, effector responses etc) in an isoform-specific as well as isotype-redundant manner. Among all the isoforms, PKC is involved predominantly in the positive regulation of proximal T cell receptor (TCR) signaling. This work presents additional functions of PKC in effector CD4+ T cells and describes functional redundancy between classical PKC isoforms. Our experimental approach encompassed in vivo experiments with genetic knock-out mouse strains, an in vivo model of autoimmune disorder as well as in vitro assays. First, a novel role of PKC as a suppressor of the Th1-transcriptional program in the early phase of Th17-directed differentiation of naïve CD4+ T cells was demonstrated. Accordingly, genetic ablation of the kinase leads to a prolongation of severe neurological symptoms in a mouse autoimmune disease model (experimental autoimmune encephalomyelitis, EAE). Secondly, the role of PKC in the positive regulation of NF-B signaling pathway was clarified. PKC participates in inactivation of CYLD, an inhibitor of the TAK1/IKK/IB axis. Molecular mechanisms of this inactivation differ between human and murine T cells.Finally, redundant functions of PKC were described. For example, PKC contributes to CYLD regulation by PKC. Furthermore, together with the isoform, PKC participates in the effective induction of Il2 gene transcription after TCR stimulation via CD3 agonistic antibodies. In the later case, however, a concomitant genetic ablation of both classical isotypes still can be overcome by CD28 co-stimulation.Taken together, presented data elucidate novel functions and explain the cross-talk between PKC isoforms in T lymphocytes.