Requirement for Tec kinases Rlk and Itk in T cell receptor signaling and immunity

T cell receptor (TCR) signaling requires activation of Zap-70 and Src famil y tyrosine kinases, but requirements for other tyrosine kinases are Less cl ear. Combined deletion in;mice of two Tec kinases, Rlk and Itk, caused mark ed defects in TCR responses including proliferation, cytokine production, a nd apoptosis in vitro and adaptive:immune responses to Toxoplasma gondii in vivo. Molecular events immediately downstream from the TCR were intact in rlk(-/-)itk(-/-) cells, but intermediate events including inositol trisphos phate production, calcium mobilization, and mitogen-activated protein kinas e activation were impaired, establishing Tec kinases as critical regulators of TCR signaling required for phospholipase C-gamma activation.