Therapy-induced antibodies to interferon-alpha 2a recognise its receptor-binding site.
Fifty-eight patients with chronic hepatitis B (HB) or C (HC) were treated with recombinant human interferon (rIFN)-alpha 2 and their sera were assayed for antibodies to rIFN-alpha 2c. Twelve of these patients produced low titres and two high titres of the antibodies. We localized the region which was recognised by the high-titre therapy-induced antibodies on the IFN molecule by testing the antibodies with a set of murine monoclonal antibodies (MoAbs) to IFN-alpha 2 in a competitive radioimmune assay (RIA). Only MoAbs with epitopes located in the amino-terminal portion of IFN-alpha 2 could inhibit the binding of radiolabelled IFN-alpha 2 by patients' sera. Our data indicate that the therapy-induced antibodies were directed to the receptor-binding domain of IFN-alpha 2 formed by amino acids (aa) 30-53. In accordance with this observation, human anti-IFN sera inhibited the binding of rIFN-alpha 2 to human cells.
Liptáková
H
H
Institute of Virology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Kontseková
E
E
Kabát
P
P
Hajnická
V
V
Oltman
M
M
Stancek
D
D
Fuchsberger
N
N
Kontsek
P
P
D000328:Adult; D000368:Aged; D000818:Animals; D000918:Antibody Specificity; D000998:Antiviral Agents / Q000276:immunology* / Q000627:therapeutic use; D001665:Binding Sites; D000939:Epitopes / Q000276:immunology*; D005260:Female; D018922:HL-60 Cells; D019694:Hepatitis B, Chronic / Q000097:blood / Q000628:therapy; D019698:Hepatitis C, Chronic / Q000097:blood / Q000628:therapy; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D051379:Mice; D011863:Radioimmunoassay; D011994:Recombinant Proteins; D013997:Time Factors
D000998:Antiviral Agents; D000939:Epitopes; D007074:Immunoglobulin G; D007370:Interferon Type I; D011994:Recombinant Proteins