TCR signaling intensity controls CD8+ T cell responsiveness to TGF-β

DGK-z is a negative regulator of TCR signaling that causes degradation of the second messenger DAG, terminating DAG-mediated activation of Ras and PKCu. Cytotoxic T cells deficient in DGK-z demonstrate enhanced effector functions in vitro and antitumor activity in vivo, perhaps because of insensitivity to inhibitory cytokines. We sought to determine whether the enhanced responsiveness of DGK-z-deficient T cells renders them insensitive to the inhibitory cytokine TGF-b and to determine how the loss of DGK-z facilitates this insensitivity. We identified decreased transcriptional and functional responses to TGF-b in CD8 + DGK-z 2/2 T cells but pre