Cutting edge: T cell-specific adapter protein inhibits T cell activation by modulating Lck activity

We previously reported the isolation of a cDNA encoding a T cell-specific a dapter protein (TSAd). Its amino acid sequence contains an SH2 domain, tyro sines in protein binding motifs, and proline-rich regions. In this report w e show that expression of TSAd is induced in normal peripheral blood T cell s stimulated with anti-CD3 mAbs or anti-CD3 plus anti-CD28 mAbs. Overexpres sion of TSAd in jurkat T cells interfered with TCR-mediated signaling by do wn-modulating anti-CD3/PMA-induced IL-2 promoter activity and anti-CD3 indu ced Ca2+ mobilization. The TCR-induced tyrosine phosphorylation of phosphol ipase C-gamma1, SH2-domain-containing leukocyte-specific phosphoprotein of 76kDa, and linker for activation of T cells was also reduced. Furthermore, TSAd inhibited Zap-70 recruitment to the CD3 zeta -chains in a dose-depende nt manner. Consistent with this, Lck kinase activity was reduced 3- to 4-fo ld in COS-7 cells transfected with both TSAd and Lck, indicating a regulato ry effect of TSAd on Lck, In conclusion, our data strongly suggest an inhib itory role for TSAd in proximal T cell activation.