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 family tyrosine kinases, but requirements for other tyrosine kinases are less clear. Combined deletion in mice of two Tec kinases, Rlk and Itk, caused marked defects in TCR responses including proliferation, cytokine production, and apoptosis in vitro and adaptive immune responses to Toxoplasma gondii in vivo. Molecular events immediately downstream from the TCR were intact in [rlk.sup.-/-][itk.sup.-/-] cells, but intermediate events including inositol trisphosphate production, calcium mobilization, and mitogen-activated protein kinase activation were impaired, establishing Tec kinases as critical regulators of TCR signaling required for phospholipase C-[Gamma] activation.
Stimulation of T lymphocytes through the TCR elicits broad responses required for proper immune function, including cell proliferation, cytokine production, and apoptosis. Key components of TCR signaling are nonreceptor tyrosine [...]