Regulatory effect of interferon-gamma and phorbol esters on the surface expression and biosynthesis of MHC class I antigens by human leukemia cells.
We have used cell surface radioiodination, biosynthetic incorporation of [35S]methionine, and flow cytometry to analyze the effects of interferon gamma (IFN-gamma) and/or phorbol esters (PMA) on the turnover and expression of class I antigens of a human leukemia B cell line. Our results demonstrated that although both IFN-gamma and PMA enhance HLA expression, they act synergistically to increase by eightfold the amount of HLA polypeptides synthesized by the acute lymphoblastic leukemia cells and acted additively to augment the cell surface expression of HLA as quantified by flow cytometry. We observed a cyclic increase or decrease in the expression of class I antigens as a function of time in cell culture. IFN-gamma and/or PMA modulated this effect inducing more cells to express HLA maximally. These results suggest that there is a physiologic limit for the expression of major histocompatibility complex class I antigens.
Guha
A
A
Department of Medicine, Connecticut Cancer Institute, University of Connecticut Health Center, Farmington 06030.
Dainiak
N
N
Freedman
M
M
Goldschneider
I
I
Cone
R E
RE
D001402:B-Lymphocytes / Q000276:immunology; D006680:HLA Antigens / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology*; D011994:Recombinant Proteins; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D011994:Recombinant Proteins; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate