ITK AND FYN MAKE INDEPENDENT CONTRIBUTIONS TO T-CELL ACTIVATION

Itk is a member of the Btk/Tec/Itk family of nonreceptor protein tyros ine kinases (PTKs), and has been implicated in T cell antigen receptor (TCR) signal transduction. Lck and Fyn are the Src-family nonreceptor PTKs that are involved in TCR signaling. To address tile question of how these members of different families of PTKs functionally contribut e to T cell development and to T cell activation, mice deficient for b oth Itk and either Lck or Fyn were generated. The Itk/Lck doubly defic ient mice exhibited a phenotype similar to that of Lck-deficient mice. The phenotype of the Itk/Fyn doubly deficient mice was similar to tha t of Itk deficient mice. However the Itk/Fyn doubly deficient mice exh ibited a more severe defect in TCR-induced proliferation of thymocytes and peripheral T cells than did mice deficient in either kinase alone . These data support the notion that Itk and Fyn both make independent contributions to TCR-induced T cell activation.