[Receptor system of interferons]

The characteristics of interferon (IFN) binding to various cells with different IFN sensitivity were studied by using (3H) leucine-labeled pure human IFN alpha from Namalwa cells and recombinant human IFN alpha 1 and alpha 2. High-affinity binding sites on IFN-sensitive cells were shown to be indispensable for IFN sensitivity and represent IFN receptors. The binding constant between IFN and the receptors was 3-10 X 10(10)M-1 which was about 50 times higher than those of insulin and epidermal growth factor. Specific binding of IFN alpha was completely inhibited by IFN beta, indicating that the receptors for IFN alpha were common to IFN beta. To analyze the relationship between different target cell specificities of IFN alpha 1 and alpha 2 and cellular binding activity of these IFNs, antiviral activities of these IFNs were compared with the cellular binding activities, suggesting that the different sensitivity of cells to IFN alpha 1 and alpha 2 was due to the different binding activity of these IFNs to the common receptors. Evidence which indicated receptor-mediated internalization of IFN was obtained. The internalization depended on temperature and energy, and degradation and secretion of internalized IFN depended on lysosome, indicating that IFN was internalized by receptor-mediated endocytosis. The possibility whether internalization is required for the establishment of IFN activity is discussed. IFN receptor has been reported to be glycoprotein with molecular weight of 140K: whether IFN receptor is heterogeneous or not is also discussed.