BIOLOGICAL-ACTIVITIES OF HUMAN TUMOR-NECROSIS-FACTOR-ALPHA AND ITS NOVEL MUTANTS

Biological activities of human tumor necrosis factor-alpha (hTNF-alpha ) and its mutants were compared. In cytotoxicity assay with L929 cells , one mutant, designated as TNF-B, showed 4.5-fold higher activity tha n TNF examined. In receptor binding assay, TNF-B had almost the same a ffinity for TNF receptors on L929 cells as hTNF-alpha. We also found t hat TNF-B retained the cytotoxicity of hTNF-alpha for HEp-2 cells. TNF -B also had two-fold higher affinity than hTNF-alpha for receptors on HEp-2 cells (only carrying hTNF-R55) and lower affinity for receptors on U937 cells (expressing mainly hTNF-R75). These results suggested th at TNF-B might still interact with the human TNF-R55 receptor,but it m ignt largely lose its ability to bind to human TNF-R75. Changes of bio logical activity of TNFs might be due to an altered affinity to the di fferent types of TNF receptor on the target cells.