Generation and Characterization of Anti-Idiotypic Antibodies Recognizing the Interferon-α Receptor: Implications for Ligand–Receptor Interactions

Monoclonal antibodies LI-1 and LI-8 against interferon-αA (IFN-α A) block IFN-αA activity and binding to its receptor, but they recognize distinct epitopes. Surprisingly, anti-idiotypic antibodies to both LI-1 and LI-8 have properties consistent with recognition of the receptor: anti-LI-1 and anti-LI-8 antibodies inhibit the binding of IFN-αA to its receptor. However, anti-LI-1 is an antagonist of IFN-αA, while anti-LI-8 is an agonist. Thus, at least some part of the epitopes on IFN-αA recognized by LI-1 and LI-8 are directly involved in receptor binding. Because these epitopes are spatially distinct, the implication is that the receptor binding site on IFN-αA must be extensive, or there are minimally two regions of IFN-αA involved in receptor interactions.