ISSN:
1365-3083
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Regulation of T-cell receptor (TCR) cell surface expression levels is probably an important mechanism by which T-cell responsiveness is controlled. Previously, two distinct pathways for TCR downregulation have been described. One is dependent on protein kinase C (PKC) and the leucine-based receptor-sorting motif (l-based motif) of the CD3γ chain but independent of tyrosine kinases, whereas the other is dependent on the tyrosine kinase activation but independent of the PKC and the CD3γl-based motif. In this study, we describe a new pathway for TCR downregulation distinct from both the PKC/CD3γl-based motif-dependent and the tyrosine kinase-dependent pathways. This pathway is dependent on ceramide-induced activation of caspases and correlate with caspase-mediated cleavage of the ζ chain. Thus, a 10–15% downregulation of the TCR was induced following the treatment of the T cells with ceramide for 4 h. A close correlation between TCR downregulation, caspase activation, and cleavage of the ζ chain was found. Furthermore, the caspase inhibitors abolished the cleavage of the ζ chain and TCR downregulation in parallel with the inhibition of the caspase activity.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1365-3083.2001.00852.x
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