A cytotoxic CD40/p55 tumor necrosis factor receptor hybrid detects CD40 ligand on herpesvirus saimiri-transformed T cells
✍ Scribed by Sigrun Hess; Roland Kurrle; Leander Lauffer; Gert Riethmüller; Hartmut Engelmann
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- English
- Weight
- 838 KB
- Volume
- 25
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
A cytotoxic CD40/p55 tumor necrosis factor receptor hybrid detects CD40 ligand on herpesvirus saimiri-transformed T cells*
The B cell activation molecule CD40 and the p55 tumor necrosis factor receptor (p55TNFR) belong to the same family of structurally conserved proteins. We constructed a chimeric receptor consisting of the CD40 extracellular and transmembrane domains and the p55TNFR intracellular domain. This receptor hybrid retained the biological activity and the ligand specificity of the respective wild-type receptor domains. Thus it exerted a marked cytotoxic effect in three different transfected cell lines after activation not only with anti-CD4O antibody but also with CD40 ligand (CD40L) in soluble and membrane-bound forms. Using hybrid-transfected baby hamster kidney cells we demonstrated that herpesvirus saimiri-transformed human CD4+ T lymphocytes constitutively express bioactive CD40 ligand on their surface. The hybrid receptor-based assay was highly specific for CD40 activating reagents and more sensitive than an assay measuring CD40-mediated B cell rescue from apoptosis. Hence CD40Ip55TNFR transfectants may be useful for dissecting CD40L-mediated events in T-B cell interactions, and also to detect a defective CD40L molecule in putative hyper-IgM syndrome patients.