EFFECT OF INTERFERON-GAMMA ON ANTIGEN-PROCESSING IN HUMAN MONOCYTES

The effect of interferon-gamma (IFN-gamma) on the ability of human mon ocytic cells to process exogenous (major histocompability complex clas s II) antigens was investigated. The processing (i.e. protein degradat ion) of antigens that were internalized via Fc gamma receptor (Fc gamm a 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 degrad ed antigen, internalized as an immune complex, at an enhanced rate. Af ter 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 pr ocessing was independent of the type of antigen, was dependent on the dose of IFN-gamma, and also occurred with normal human peripheral mono cytes. Analysis of the degraded peptides by high-pressure liquid chrom atography indicated that some of the peptides generated in the IFN-gam ma-treated cells were both quantitatively and qualitatively different from the peptides generated in untreated cells. These data suggest tha t IFN-gamma modulates the way in which antigens, internalized through Fc receptors as immune complexes, are processed. Additionally, the res ults imply that decreases in the rate of antigen processing may lead t o more efficient antigen presentation.