Identification of a 60-kD tumor necrosis factor (TNF) receptor as the major signal transducing component in TNF responses.
We describe here a monoclonal antibody (H398) that immunoprecipitates a human 60-kD tumor necrosis factor (TNF) membrane receptor (p60) and competes with TNF binding to p60 but not to p85 TNF receptors. Despite partial inhibition of TNF binding capacity of cells coexpressing both TNF receptor molecules, H398 uniformly and completely inhibits very distinct TNF responses on a variety of cell lines. These data suggest a limited structural heterogeneity in those components actually contributing to TNF responsiveness and identify p60 as a common receptor molecule essential for TNF signal transduction. As H398 is a highly effective TNF antagonist in vitro, it might be useful as a therapeutic agent in the treatment of TNF-mediated acute toxicity.
Thoma
B
B
Clinical Research Group, University of Göttingen, Federal Republic of Germany.
Grell
M
M
Pfizenmaier
K
K
Scheurich
P
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002460:Cell Line; D006801:Humans; D051379:Mice; D008970:Molecular Weight; D011956:Receptors, Cell Surface / Q000032:analysis / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha