Functional Characterization of Monoclonal Antibodies to Interferon-Tau

Abstract

Interferon tau (IFNτ) produces an array of biological effects, including antiluteolytic, antiviral, antiproliferative and immunomodulatory activities, without the consequent cytotoxicity associated with other type I IFNs. Four anti-IFNτ monoclonal antibodies (MAbs) have been characterized by determining regional epitopes and observation of their effects on IFNτ binding, antiviral and antiproliferative activity. Using an enzyme-linked immunoadsorbent assay (ELISA) developed against six overlapping synthetic peptides representing the entire linear sequence of IFNτ, three antibodies, HL-98, HL-100 and HL-127, were found to react with the carboxy terminal peptide, while HL-129 bound the penultimate amino terminal peptide. Binding studies indicated that MAbs directed against either region could effectively inhibit the binding of alkaline phosphatase labeled IFNτ to cells expressing type I IFN receptors. While only two of the MAbs significantly reversed IFNτ-induced growth inhibition, the antiviral activity of IFNτ was significantly inhibited by MAbs that bound the amino and carboxy termini, confirming the functional importance of these domains in the binding and subsequent activity of IFNτ.