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

V. Sundvold, K. M. Torgersen, N. H. Post, F. Marti, P. D. King, J. A. Rottingen, A. Spurkland, T. Lea

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

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-γ1, 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 CD3ζ-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.

Original languageEnglish
Pages (from-to)2927-2931
Number of pages5
JournalJournal of Immunology
Volume165
Issue number6
DOIs
StatePublished - Sep 15 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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