Effect of interferon-gamma on antigen processing in human monocytes.
The effect of interferon-gamma (IFN-gamma) on the ability of human monocytic cells to process exogenous (major histocompability complex class II) antigens was investigated. The processing (i.e. protein degradation) of antigens that were internalized via Fc gamma receptor (Fc gamma R) was followed for various times after treatment of cells with IFN-gamma. THP-1 cells that had been treated with IFN-gamma for 4 h degraded antigen, internalized as an immune complex, at an enhanced rate. After 24 h of IFN-gamma treatment the rate of processing was similar to untreated cells. Unexpectedly, in cells which had been treated for 48-72 h there was a significant decrease in the rate of processing of the exogenous antigen. These effects were not due to changes in the rate of internalization of immune complex. The inhibition of the rate of processing was independent of the type of antigen, was dependent on the dose of IFN-gamma, and also occurred with normal human peripheral monocytes. Analysis of the degraded peptides by high-pressure liquid chromatography indicated that some of the peptides generated in the IFN-gamma-treated cells were both quantitatively and qualitatively different from the peptides generated in untreated cells. These data suggest that IFN-gamma modulates the way in which antigens, internalized through Fc receptors as immune complexes, are processed. Additionally, the results imply that decreases in the rate of antigen processing may lead to more efficient antigen presentation.
Nadler
S G
SG
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121.
Rankin
B M
BM
Moran-Davis
P
P
Cleaveland
J S
JS
Kiener
P A
PA
D000936:Antigen-Antibody Complex / Q000378:metabolism; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000941:Antigens / Q000378:metabolism*; D002460:Cell Line; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D009000:Monocytes / Q000276:immunology*; D010449:Peptide Mapping; D017452:Receptors, IgG / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000276:immunology
D000936:Antigen-Antibody Complex; D000941:Antigens; D006680:HLA Antigens; D017452:Receptors, IgG; D012710:Serum Albumin, Bovine; D007371:Interferon-gamma