Related Experiment Videos
T cell-specific adapter protein inhibits T cell activation by modulating Lck activity
V Sundvold1, K M Torgersen, N H Post
1Institute of Immunology, The National Hospital, Oslo, Norway.
Journal of Immunology (Baltimore, Md. : 1950)
|September 7, 2000
Summary
T cell-specific adapter protein (TSAd) expression inhibits T cell receptor signaling. Overexpression of TSAd down-modulates key signaling pathways, suggesting an inhibitory role in T cell activation.
Area of Science:
- Immunology
- Molecular Biology
- Cell Signaling
Background:
- T cell-specific adapter protein (TSAd) is a newly identified protein.
- TSAd possesses an SH2 domain, tyrosines in protein binding motifs, and proline-rich regions.
Purpose of the Study:
- To investigate the role of TSAd in T cell activation.
- To elucidate the molecular mechanisms by which TSAd affects T cell receptor (TCR) signaling.
Main Methods:
- Studied TSAd expression in peripheral blood T cells stimulated with anti-CD3 and anti-CD28 antibodies.
- Overexpressed TSAd in Jurkat T cells to assess its impact on TCR-mediated signaling.
- Analyzed TCR-induced signaling events including IL-2 promoter activity, calcium mobilization, and tyrosine phosphorylation of key signaling molecules.
- Investigated TSAd's effect on Zap-70 recruitment and Lck kinase activity.
Main Results:
- TSAd expression is induced upon T cell activation.
- Overexpression of TSAd impairs TCR-mediated IL-2 production and calcium influx.
- TSAd reduces the phosphorylation of phospholipase C-gamma1, SLP-76, and LAT.
- TSAd inhibits Zap-70 recruitment to CD3zeta chains and reduces Lck kinase activity.
Conclusions:
- TSAd plays an inhibitory role in proximal T cell activation.
- TSAd negatively regulates TCR signaling by interfering with key signaling molecules and kinases.