Selective inhibition of CTL activation by a dipalmitoyl-phospholipid that prevents the recruitment of signaling molecules to lipid rafts.

Détails

ID Serval
serval:BIB_5113065AD330
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Selective inhibition of CTL activation by a dipalmitoyl-phospholipid that prevents the recruitment of signaling molecules to lipid rafts.
Périodique
FASEB Journal
Auteur(s)
Legler D.F., Doucey M.A., Cerottini J.C., Bron C., Luescher I.F.
ISSN
0892-6638[print], 0892-6638[linking]
Statut éditorial
Publié
Date de publication
2001
Volume
15
Numéro
9
Pages
1601-1603
Langue
anglais
Résumé
Antigen-specific T-cell activation implicates a redistribution of plasma membrane-bound molecules in lipid rafts, such as the coreceptors CD8 and CD4, the Src kinases Lek and Fyn, and the linker for activation of T cells (LAT), that results in the formation of signaling complexes. These molecules partition in lipid rafts because of palmitoylation of cytoplasmic, membrane proximal cysteines, which is essential for their functional integrity in T-cell activation. Here, we show that exogenous dipalmitoyl-phosphatidylethanolamine (DPPE), but not the related unsaturated dioleoyl-phosphatidylethanolamine (DOPE), partitions in lipid rafts. DPPE inhibits activation of CD8(+) T lymphocytes by sensitized syngeneic antigen-presenting cells or specific major histocompatibility complex (MHC) peptide tetramers, as indicated by esterase release and intracellular calcium mobilization. Cytotoxic, T lymphocyte (CTL)-target cell conjugate formation is not affected by DPPE, indicating that engagement of the T-cell receptor by its cognate ligand is intact in lipid-treated cells. In contrast to other agents known to block raft-dependent signaling, DPPE efficiently inhibits the MHC peptide-induced recruitment of palmitoylated signaling molecules to lipid rafts and CTL activation without affecting cell viability or lipid raft integrity.
Mots-clé
Animals, Glycerophospholipids/pharmacology, Humans, Lymphocyte Activation/drug effects, Membrane Microdomains/drug effects, Membrane Microdomains/physiology, Mice, Phosphatidylethanolamines/pharmacology, Signal Transduction, T-Lymphocytes, Cytotoxic/drug effects, T-Lymphocytes, Cytotoxic/physiology, Tumor Cells, Cultured
Pubmed
Web of science
Création de la notice
28/01/2008 12:19
Dernière modification de la notice
03/03/2018 17:10
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