Physicochemical and antigenic properties of synthetic fragments of human leukocyte interferon.

Abstract

Although interferons (IFNs) were originally described as proteins conferring antiviral resistance to eukaryotic cells1, various additional biological effects have since been attributed to them, including inhibition of cell proliferation and modulation of the immune response2. More recently it was recognized that interferons from different sources have similar amino acid sequences, suggesting their evolutionary relationship. When the sequences of human interferons of the α and β type were aligned to give maximum homology, a largely conserved region was found near the carboxyl terminus of the molecules3,4. The homology of human leukocyte IFN-α1 and human fibroblast interferon between positions 111 and 166, for instance, was 40%. As conservation of segments of polypeptide chains during evolution may indicate their functional importance5, we synthesized three carboxyl-terminal fragments of human IFN-α1 (ref. 6) ranging in size from 33 to 96 amino acid residues. If the folding of these fragments was similar to that of the corresponding segments in the intact protein, it was conceivable that they had biological activity and that antibodies raised against the synthetic fragments cross-reacted with natural interferon. Such antibodies could be used for the affinity purification of human interferon produced in bacteria and for radioimmunoassays. As we show here, none of the fragments had antiviral activity. A mouse monoclonal antibody prepared against a 56-residue fragment also bound intact IFN-α1 and IFN-α2 without neutralizing their antiviral effect. Thus, this antibody, directed against a largely conserved region, may show substantial cross-reactivity within the interferon protein family.