Development of improved soluble inhibitors of FasL and CD40L based on oligomerized receptors.

Détails

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Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_69A67AAF39A6
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Development of improved soluble inhibitors of FasL and CD40L based on oligomerized receptors.
Périodique
Journal of Immunological Methods
Auteur(s)
Holler N., Kataoka T., Bodmer J.L., Romero P., Romero J., Deperthes D., Engel J., Tschopp J., Schneider P.
ISSN
0022-1759 (Print)
ISSN-L
0022-1759
Statut éditorial
Publié
Date de publication
2000
Volume
237
Numéro
1-2
Pages
159-173
Langue
anglais
Résumé
TNF receptor family members fused to the constant domain of immunoglobulin G have been widely used as immunoadhesins in basic in vitro and in vivo research and in some clinical applications. In this study, we assemble soluble, high avidity chimeric receptors on a pentameric scaffold derived from the coiled-coil domain of cartilage oligomeric matrix protein (COMP). The affinity of Fas and CD40 (but not TNFR-1 and TRAIL-R2) to their ligands is increased by fusion to COMP, when compared to the respective Fc chimeras. In functional assays, Fas:COMP was at least 20-fold more active than Fas:Fc at inhibiting the action of sFasL, and CD40:COMP could block CD40L-mediated proliferation of B cells, whereas CD40:Fc could not. In conclusion, members of the TNF receptor family can display high specificity and excellent avidity for their ligands if they are adequately multimerized.
Mots-clé
Animals, Antigens, CD40/metabolism, Antigens, CD95/metabolism, B-Lymphocytes/cytology, B-Lymphocytes/drug effects, CD40 Ligand, Extracellular Matrix Proteins/genetics, Extracellular Matrix Proteins/metabolism, Fas Ligand Protein, Glycoproteins/genetics, Glycoproteins/metabolism, Humans, Jurkat Cells, Ligands, Lymphocyte Activation/drug effects, Membrane Glycoproteins/antagonists &amp, inhibitors, Membrane Glycoproteins/metabolism, Mice, Mice, Knockout, Receptors, Fc/genetics, Receptors, Fc/metabolism, Receptors, Tumor Necrosis Factor/genetics, Receptors, Tumor Necrosis Factor/metabolism, Recombinant Fusion Proteins/genetics, Recombinant Fusion Proteins/metabolism, Solubility, Tumor Cells, Cultured
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/01/2008 12:28
Dernière modification de la notice
20/08/2019 15:24
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