A monoclonal antibody to the NH2-terminal segment of human IFN-gamma selectively interferes with the antiproliferative activity of the lymphokine.
To gain more information about the relationship between the structure of IFN-gamma and its activity, a peptide corresponding to a hydrophilic peak between amino acids 4 and 16 was used to immunize mice and generate mAb. mAb IGMB-15 reacts to both native and rIFN-gamma and neutralizes the antiproliferative activity of IFN-gamma without affecting its antiviral activity or its ability to up-regulate HLA-DR Ag expression. Moreover, we observed that mAb IGMB-15 was unable to inhibit the binding of radiolabeled IFN-gamma to its cellular receptor. These findings show that the NH2-terminal region may somehow be involved in the biologic activity of IFN-gamma. Besides, the capability of mAb IGMB-15 to inhibit the antiproliferative but not the antiviral activity of IFN-gamma in the same cell (HEp-2) suggests the presence of different elements involved in signal transduction, which may account for the multiple activities of the lymphokine.
Caruso
A
A
Institute of Microbiology, University of Brescia, Italy.
Tiberio
L
L
De Rango
C
C
Bonfanti
C
C
Flamminio
G
G
Gribaudo
G
G
Monti
E
E
Viani
E
E
Manca
N
N
Garotta
G
G
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005260:Female; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology*; D011994:Recombinant Proteins; D013329:Structure-Activity Relationship
D000911:Antibodies, Monoclonal; D006684:HLA-DR Antigens; D010446:Peptide Fragments; D011994:Recombinant Proteins; D007371:Interferon-gamma