The Carboxyterminal Domains of Human IFN-α2 and IFN-α8 Are Antigenically Homologous

Abstract

The antigenic properties of human hybrid IFN-α8(60)/α1(92)/α 8 were compared with those of human IFN alpha 1 and IFN-α 2 using monoclonal antibodies (mAb). Hybrid IFN demonstrated a significantly closer antigenic relationship to the subtype α2 than to the subtype α1. In particular, high homology was observed between antigenic structures located in the C-terminal domains(93–166) of IFN-α8 and IFN-α2, whereas the corresponding N-terminal receptor-binding domains (30–53) showed distinct antigenic characteristics. The 100% homology between IFN-α8 and IFN-α2 in the region 114–131 (helix D) indicated the role of this region in formation of the common antigenic structure. In IFN-α 8/1/8, this shared antigenic structure was important for antiviral activity and exhibited immunodominant properties, consistent with functional and antigenic properties of the corresponding structure in IFN-α2. Based on this antigenic homology, we suggest that IFN-α8 and IFN-α2 are evolutionarily more closely related to each other than to IFN-α1. This study will contribute to a better understanding of evolutionary events in the human IFN-α family.