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

Doucey, Marie-Agnès; Legler, Daniel F.; Boucheron, Nicole; Cerottini, Jean-Charles; Bron, Claude; Luescher, Immanuel F.

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

Dateien

Doucey_0-366245.pdfGröße: 1.05 MBDownloads: 287

Datum

2001

Autor:innen

Doucey, Marie-Agnès

Legler, Daniel F.

Boucheron, Nicole

Cerottini, Jean-Charles

Bron, Claude

Luescher, Immanuel F.

Open Access-Veröffentlichung

Open Access Green

Sammlungen

Biologie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

European Journal of Immunology. 2001, 31(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

Zusammenfassung

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^d-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^d-PbCS(ABA) complexes co-engaging TCR and CD8. Using TCR ligand photo-cross-linking, we find that monomeric K^d-PbCS(ABA) complexes promote association of TCR/CD3 with CD8/p56^lck. Dimerization of these adducts results in activation of p56lck in lipid rafts, where phosphatases are excluded. Additional cross-linking further increases p56^lck 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^d 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^lck takes place in rafts, both reagents, though in different ways, impair coupling of p56^lck to TCR, thereby inhibiting the initial and essential activation of p56^lck induced by cross-linking of engaged TCR.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Zitieren

ISO 690

DOUCEY, Marie-Agnès, Daniel F. LEGLER, Nicole BOUCHERON, Jean-Charles CEROTTINI, Claude BRON, Immanuel F. LUESCHER, 2001. CTL activation is induced by cross-linking of TCR/MHC-peptide-CD8/p56lck adducts in rafts. In: European Journal of Immunology. 2001, 31(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

BibTex

@article{Doucey2001activ-36630,
  year={2001},
  doi={10.1002/1521-4141(200105)31:5<1561::AID-IMMU1561>3.0.CO;2-W},
  title={CTL activation is induced by cross-linking of TCR/MHC-peptide-CD8/p56lck adducts in rafts},
  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.}
}

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