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-alpha A (IFN-alpha A) block IFN-alpha A 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-alpha A to its receptor. However, anti-LI-1 is an antagonist of IFN-alpha A, while anti-LI-8 is an agonist. Thus, at least some part of the epitopes on IFN-alpha A 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-alpha A must be extensive, or there are minimally two regions of IFN-alpha A involved in receptor interactions.