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

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

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LEGLER, Daniel F., Marie-Agnès DOUCEY, Jean-Charles CEROTTINI, Claude BRON, Immanuel F. LUESCHER, 2001. Selective inhibition of CTL activation by a dipalmitoyl-phospholipid that prevents the recruitment of signaling molecules to lipid rafts. In: The FASEB Journal. 15(9), pp. 1601-1603. ISSN 0892-6638. eISSN 1530-6860

@article{Legler2001-05-18Selec-35556, title={Selective inhibition of CTL activation by a dipalmitoyl-phospholipid that prevents the recruitment of signaling molecules to lipid rafts}, year={2001}, doi={10.1096/fj.00-0841fje}, number={9}, volume={15}, issn={0892-6638}, journal={The FASEB Journal}, pages={1601--1603}, author={Legler, Daniel F. and Doucey, Marie-Agnès and Cerottini, Jean-Charles and Bron, Claude and Luescher, Immanuel F.} }

Doucey, Marie-Agnès Doucey, Marie-Agnès Cerottini, Jean-Charles 2001-05-18 2016-10-13T09:20:39Z Luescher, Immanuel F. Bron, Claude Cerottini, Jean-Charles eng Luescher, Immanuel F. 2016-10-13T09:20:39Z Selective inhibition of CTL activation by a dipalmitoyl-phospholipid that prevents the recruitment of signaling molecules to lipid rafts 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 Lck 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<sup>+</sup> 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 raftdependent 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. Bron, Claude Legler, Daniel F. Legler, Daniel F.

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