1. Binding and activity of all human alpha interferon subtypes
- Author
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Eyal Kalie, Renne Abramovich, Sidney Pestka, Sara Crisafulli-Cabatu, Gideon Schreiber, Gina DiGioia, Karlene Moolchan, and Thomas B. Lavoie
- Subjects
Immunology ,Molecular Sequence Data ,Alpha interferon ,Plasma protein binding ,Biology ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Interferon ,Cell Line, Tumor ,medicine ,Immunology and Allergy ,Potency ,Humans ,Amino Acid Sequence ,Receptor ,Molecular Biology ,030304 developmental biology ,Cell Proliferation ,Receptors, Interferon ,0303 health sciences ,Sequence Homology, Amino Acid ,Interferon-alpha ,Biological activity ,Hematology ,Ligand (biochemistry) ,Virology ,Affinities ,030220 oncology & carcinogenesis ,medicine.drug ,Protein Binding - Abstract
Vertebrates have multiple genes encoding Type I interferons (IFN), for reasons that are not fully understood. The Type I IFN appear to bind to the same heterodimeric receptor and the subtypes have been shown to have different potencies in various experimental systems. To put this concept on a quantitative basis, we have determined the binding affinities and rate constants of 12 human Alpha-IFN subtypes to isolated interferon receptor chains 1 and 2. Alpha-IFNs bind IFNAR1 and IFNAR2 at affinities of 0.5-5 μM and 0.4-5 nM respectively (except for IFN-alpha1 - 220 nM). Additionally we have examined the biological activity of these molecules in several antiviral and antiproliferative models. Particularly for antiproliferative potency, the binding affinity and activity correlate. However, the EC50 values differ significantly (1.5 nM versus 0.1 nM for IFN-alpha2 in WISH versus OVCAR cells). For antiviral potency, there are several instances where the relationship appears to be more complicated than simple binding. These results will serve as a point of reference for further understanding of this multiple ligand/receptor system.
- Published
- 2011