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CTL activation is induced by cross-linking of TCR/MHC-peptide-CD8/p56lck adducts in rafts

CTL activation is induced by cross-linking of TCR/MHC-peptide-CD8/p56lck adducts in rafts

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DOUCEY, Marie-Agnès, Daniel F. LEGLER, Nicole BOUCHERON, Jean-Charles CEROTTINI, Claude BRON, Immanuel F. LUESCHER, 2001. <i>CTL activation is induced by cross-linking of TCR/MHC-peptide-CD8/p56lck adducts in rafts</i>. In: European Journal of Immunology. <b>31</b>(5), pp. 1561-1570. ISSN 0014-2980. eISSN 1521-4141. Available under: doi: 10.1002/1521-4141(200105)31:5<1561::AID-IMMU1561>3.0.CO;2-W

@article{Doucey2001activ-36630, title={CTL activation is induced by cross-linking of TCR/MHC-peptide-CD8/p56lck adducts in rafts}, year={2001}, doi={10.1002/1521-4141(200105)31:5<1561::AID-IMMU1561>3.0.CO;2-W}, number={5}, volume={31}, issn={0014-2980}, journal={European Journal of Immunology}, pages={1561--1570}, author={Doucey, Marie-Agnès and Legler, Daniel F. and Boucheron, Nicole and Cerottini, Jean-Charles and Bron, Claude and Luescher, Immanuel F.} }

To investigate the role of the coreceptor CD8 and lipid rafts in cytotoxic T lymphocyte (CTL) activation, we used soluble mono-and multimeric H-2K<sup>d</sup>-peptide complexes and cloned S14 CTL specific for a photoreactive derivative of the Plasmodium berghei circumsporozoite (PbCS) peptide 252–260 [PbCS(ABA)]. We report that activation of CTL in suspension requires multimeric K<sup>d</sup>-PbCS(ABA) complexes co-engaging TCR and CD8. Using TCR ligand photo-cross-linking, we find that monomeric K<sup>d</sup>-PbCS(ABA) complexes promote association of TCR/CD3 with CD8/p56<sup>lck</sup>. Dimerization of these adducts results in activation of p56lck in lipid rafts, where phosphatases are excluded. Additional cross-linking further increases p56<sup>lck</sup> kinase activity, induces translocation of TCR/CD3 and other signaling molecules to lipid rafts and intracellular calcium mobilization. These events are prevented by blocking Src kinases or CD8 binding to TCR-associated K<sup>d</sup> molecules, indicating that CTL activation is initiated by cross-linking of CD8-associated p56lck. They are also inhibited by methyl-β-cyclodextrin, which disrupts rafts and by dipalmitoyl phosphatidylethanolamine, which interferes with TCR signaling. Because efficient association of CD8 and p56<sup>lck</sup> takes place in rafts, both reagents, though in different ways, impair coupling of p56<sup>lck</sup> to TCR, thereby inhibiting the initial and essential activation of p56<sup>lck</sup> induced by cross-linking of engaged TCR. Doucey, Marie-Agnès 2017-01-12T10:26:57Z Boucheron, Nicole 2017-01-12T10:26:57Z Bron, Claude Bron, Claude Luescher, Immanuel F. Cerottini, Jean-Charles Boucheron, Nicole 2001 Cerottini, Jean-Charles Legler, Daniel F. Luescher, Immanuel F. Legler, Daniel F. CTL activation is induced by cross-linking of TCR/MHC-peptide-CD8/p56lck adducts in rafts Doucey, Marie-Agnès eng

Dateiabrufe seit 12.01.2017 (Informationen über die Zugriffsstatistik)

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