A cytotoxic CD40/p55 tumor necrosis factor receptor hybrid detects CD40 ligand on herpesvirus saimiri‐transformed T cells

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Abstract
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‐CD40 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 CD40/p55TNFR 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.