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

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.

journal_name

J Immunol Methods

authors

Holler N,Kataoka T,Bodmer JL,Romero P,Romero J,Deperthes D,Engel J,Tschopp J,Schneider P

doi

10.1016/s0022-1759(99)00239-2

keywords:

subject

Has Abstract

pub_date

2000-04-03 00:00:00

pages

159-73

issue

1-2

eissn

0022-1759

issn

1872-7905

pii

S0022-1759(99)00239-2

journal_volume

237

pub_type

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