Format

Send to

Choose Destination
J Immunol Methods. 2000 Apr 3;237(1-2):159-73.

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

Author information

1
Institute of Biochemistry, University of Lausanne, Ch. des Boveresses 155, CH-1066, Epalinges, Switzerland.

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.

PMID:
10725460
DOI:
10.1016/s0022-1759(99)00239-2
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center