DIFFERENTIAL NEUTRALIZING ACTIVITY OF HUMAN-ANTIBODIES IN INTERFERON ANTIVIRAL AND NATURAL-KILLER-CELL BIOASSAYS

The ability of interferon-alpha (IFN-alpha) to augment the cytotoxicit y of human natural killer (NK) cells was used to probe the neutralizat ion capacity of human antibodies to IFN-alpha. Sera from patients trea ted with IFN-alpha were tested for antibodies that could bind to IFN-a lpha, neutralize IFN-alpha antiviral activity, or neutralize INF-alpha -mediated augmentation of NK cytolytic activity, The NK-augmenting act ivity of IFN-alpha was measured in a chromium-release cytotoxicity ass ay using K562 targets and human peripheral blood mononuclear cells in the presence of a constant amount of antibody from patients treated wi th IFN-alpha. Neutralization of IFN-alpha-mediated antiviral activity did not correlate with neutralization of NK augmentation, However, all sera that neutralized a biologic activity of IFN-alpha also bound IFN -alpha. Conversely, sera that did not bind to IFN-alpha also did not n eutralize either biologic activity, The data suggest that some immunog enic epitopes of IFN-alpha reside in distinct domains that mediate dif ferent biologic activities of IFN-alpha. The identification of neutral izing antibodies for the NK immunomodulating function of IFN-alpha but not antiviral function suggests that assessment of antiviral neutrali zation alone may be an incomplete evaluation of the potential signific ance of binding antibodies that occur subsequent to the administration of therapeutic IFNs.