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The Journal of Immunology, 00, 165: 2927-2931.
Copyright © 00 by The American Association of Immunologists

CUTTING EDGE

Cutting Edge: T Cell-Specific Adapter Protein Inhibits T Cell Activation by Modulating Lck Activity

Vibeke Sundvold*, Knut Martin Torgersen{dagger}, Nicholas H. Post§, Francesc Marti§, Philip D. King§,¶, John Arne Røttingen{ddagger}, Anne Spurkland* and Tor Lea1,*

* Institute of Immunology, The National Hospital, Oslo, Norway; Departments of {dagger} Anatomy and {ddagger} Physiology, University of Oslo, Oslo, Norway; § Immunology and Inflammation, Hospital for Special Surgery, Weill Medical College of Cornell University, and Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10021

We previously reported the isolation of a cDNA encoding a T cell-specific adapter protein (TSAd). Its amino acid sequence contains an SH2 domain, tyrosines in protein binding motifs, and proline-rich regions. In this report we show that expression of TSAd is induced in normal peripheral blood T cells stimulated with anti-CD3 mAbs or anti-CD3 plus anti-CD28 mAbs. Overexpression of TSAd in Jurkat T cells interfered with TCR-mediated signaling by down-modulating anti-CD3/PMA-induced IL-2 promoter activity and anti-CD3 induced Ca2+ mobilization. The TCR-induced tyrosine phosphorylation of phospholipase C-{gamma}1, 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-dependent manner. Consistent with this, Lck kinase activity was reduced 3- to 4-fold in COS-7 cells transfected with both TSAd and Lck, indicating a regulatory effect of TSAd on Lck. In conclusion, our data strongly suggest an inhibitory role for TSAd in proximal T cell activation.




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