TSAd/Lad is a T cell adaptor molecule involved in p^56lck-mediated T cell activation. To investigate the functions of TSAd in T cells, we generated transgenic (TG) mice ex-pressing the SH2 domain of TSAd (TSAd-SH2) under the control of the p^56lck proximal promoter. In T cells from TSAd-SH2 TG mice, T cell receptor (TCR)-mediated early signaling events, such as Ca²⁺ flux and ERK activation, were normal; however, late activation events, such as IL-2 production and proliferation, were significantly reduced. Moreover, TCR-induced cell adhesion to extracellular matrix (ECM) proteins and migration through ECM proteins were defective in T cells from TSAd-SH2 TG mice. Furthermore, the contact hypersensitivity (CHS) reaction, an inflammatory response mainly mediated by T helper 1 (Th1) cells, was inhibited in TSAd-SH2 TG mice. Taken together, these results show that TSAd, particularly the SH2 domain of TSAd, is essential for the effector functions of T cells.

Keywords: adhesion, Lad, migration, SH2 domain, TSAd