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  Cholesterol and Sphingomyelin Drive Ligand-independent T-cell Antigen Receptor Nanoclustering

Molnár, E., Swamy, M., Holzer, M., Beck-García, K., Worch, R., Thiele, C., et al. (2012). Cholesterol and Sphingomyelin Drive Ligand-independent T-cell Antigen Receptor Nanoclustering. The Journal of Biological Chemistry, 287, 42664-42674.

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Datensatz-Permalink: https://hdl.handle.net/11858/00-001M-0000-002B-8CB7-A Versions-Permalink: https://hdl.handle.net/11858/00-001M-0000-002B-8CB8-8
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 Urheber:
Molnár, Eszter1, Autor
Swamy, Mahima2, Autor           
Holzer, Martin, Autor
Beck-García, Katharina1, Autor
Worch, Remigiusz, Autor
Thiele, Christoph, Autor
Guigas, Gernot, Autor
Boye, Kristian, Autor
Leuscher, Immanuel F., Autor
Schwille, Petra, Autor
Schubert, Rolf, Autor
Schamel, Wolfgang W. A.2, Autor           
Affiliations:
1Max Planck Society, ou_persistent13              
2Research Group and Chair of Molecular Immunology of the University of Freiburg, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243645              

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 Zusammenfassung: The T-cell antigen receptor (TCR) exists in monomeric and nanoclustered forms independently of antigen binding. Although the clustering is involved in the regulation of T-cell sensitivity, it is unknown how the TCR nanoclusters form. We show that cholesterol is required for TCR nanoclustering in T cells and that this clustering enhances the avidity but not the affinity of the TCR-antigen interaction. Investigating the mechanism of the nanoclustering, we found that radioactive photocholesterol specifically binds to the TCRβ chain in vivo. In order to reduce the complexity of cellular membranes, we used a synthetic biology approach and reconstituted the TCR in liposomes of defined lipid composition. Both cholesterol and sphingomyelin were required for the formation of TCR dimers in phosphatidylcholine-containing large unilamellar vesicles. Further, the TCR was localized in the liquid disordered phase in giant unilamellar vesicles. We propose a model in which cholesterol and sphingomyelin binding to the TCRβ chain causes TCR dimerization. The lipid-induced TCR nanoclustering enhances the avidity to antigen and thus might be involved in enhanced sensitivity of memory compared with naive T cells. Our work contributes to the understanding of the function of specific nonannular lipid-membrane protein interactions.

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Sprache(n): eng - English
 Datum: 2012-12-14
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: eDoc: 634070
 Art des Abschluß: -

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Titel: The Journal of Biological Chemistry
  Alternativer Titel : J. Biol. Chem.
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 287 Artikelnummer: - Start- / Endseite: 42664 - 42674 Identifikator: -