Comparison of augmentation of human natural killer cell cytotoxicity by interferon-alpha subtypes.
The capacity of 3 interferon-alpha (IFN-alpha) subtypes, alpha 1, alpha 2 and alpha 4, to augment human natural killer cytotoxicity after exposure in vitro was shown to be dose-dependent and to differ according to subtype. With 10(2) IU/ml, the lowest IFN concentration used, stimulation of NK activity by IFN-alpha 2 was consistently and significantly greater than by IFN-alpha 4 or IFN-alpha 1. An IFN-alpha analogue in which arginine and lysine residues 121 and 122 were replaced by 2 leucines was generated by site-directed in vitro mutagenesis of the IFN-alpha 4 gene; at equivalent concentrations of antiviral activity, this analogue was 10-fold less effective in NK stimulation. There was a lack of correlation between NK-stimulatory and other activities of the IFN-alpha subtypes and the mutant, suggesting that different biological activities may be mediated by different regions of the IFN-alpha molecule.
Verhagen
A
A
Centre for Molecular Biology and Medicine, Monash University, Melbourne, Victoria, Australia.
Mackay
I R
IR
Rowley
M
M
Tymms
M
M
D003602:Cytotoxicity, Immunologic; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D007694:Killer Cells, Natural; D016297:Mutagenesis, Site-Directed; D013997:Time Factors
D007370:Interferon Type I