Development of improved soluble inhibitors of FasL and CD40L based on oligomerized receptors.
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State: Public
Version: author
State: Public
Version: author
Serval ID
serval:BIB_69A67AAF39A6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Development of improved soluble inhibitors of FasL and CD40L based on oligomerized receptors.
Journal
Journal of Immunological Methods
ISSN
0022-1759 (Print)
ISSN-L
0022-1759
Publication state
Published
Issued date
2000
Volume
237
Number
1-2
Pages
159-173
Language
english
Abstract
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.
Keywords
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 &, 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
Yes
Create date
28/01/2008 12:28
Last modification date
20/08/2019 15:24