T cell activation is a critical process in initiating adaptive immune response since only through this process the naive antigen specific T cells differentiate into armed effector T cells that mediate the actual immune response. During T cell activation, naive T cells undergo clonal expansion and acquire the capability to kill target cells infected with pathogens or produce cytokines essential for regulating immune response. Inappropriate activation or inactivation of T cells leads to autoimmunity or severe immunodeficiencies. PKC-theta is selectively expressed in T cells and required for mediating T cell activation process. Mice deficient in PKC-theta exhibit defects in T cell activation, survival and activation-induced cell death. PKC-theta selectively translocates to immunological synapse and mediates the signals required for activation of NF-kappaB, AP1 and NFAT that are essential for T cell activation. Furthermore, PKC-theta-/- mice displayed multiple defects in the development of T cell-mediated immune responses in vivo. PKC-theta is thus a critical molecule that regulates T cell function at multiple stages in T cell-mediated immune responses in vivo.