LIGAND PASSING - THE 75-KDA TUMOR-NECROSIS-FACTOR (TNF) RECEPTOR RECRUITS TNF FOR SIGNALING BY THE 55-KDA TNF RECEPTOR

To understand the role of the 75-kDa tumor necrosis factor (TNF) receptor in non-lymphoid cells, the cytotoxic signaling and ligand binding activities of the 55-kDa (TNF-R1) and 75-kDa (TNF-R2) TNF receptors were investigated using agonist and antagonist antibodies specific for the two receptor types. This study indicates that although TNF-R2 can significantly reduce the TNF concentration required for cell killing, the mechanism by which this is accomplished is not through the generation of an intracellular signal by TNF-R2. Instead, TNF-R2 regulates the rate of TNF association with TNF-R1, possibly by increasing the local concentration of TNF at the cell surface through rapid ligand association and dissociation. We propose that other cell-surface receptors, such as the low affinity p75 nerve growth factor receptor, may utilize an analogous ''ligand passing'' mechanism.