Translational control of MHC class II I-A molecules by IFN-gamma.
MHC class II molecules are expressed in a limited number of cell types, including B lymphocytes and macrophages (M phi). IFN-gamma increases the surface expression of class II molecules in a murine B cell line without inducing detectable changes in either I-A or I-A mRNA levels. In bone marrow-derived M phi, IFN-gamma causes an increase in class II expression at both the mRNA and surface levels. In addition to the increase in transcription rates described for M phi, IFN-gamma increases the rate of synthesis of IA alpha and IA beta proteins and the ribosome loading for both mRNA molecules in both cell types. Interestingly, there is a significant peak of free I-A mRNA in noninduced cells. Therefore, IFN-gamma regulates the expression of MHC class II molecules at the translational level in both B cells and M phi and, as already reported, at the transcriptional level only in M phi. The actual mechanism of regulation causes changes in the translation initiation rates in both cell types, as demonstrated by an increase in ribosome loading in polysome gradients.
Department de Fisiologia (Immunologia), Facultat de Biologia and Fundacio August Pi i Sunyer, Campus de Bellvitge, Universitat de Barcelona, Spain.
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E
Goñalons
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M
Barrachina
J A
JA
García-Sanz
A
A
Celada
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D005802:Genes, MHC Class II / Q000187:drug effects / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D007371:Interferon-gamma / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects / Q000276:immunology*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D012260:Ribonucleases; D015534:Trans-Activators / Q000502:physiology; D014407:Tumor Cells, Cultured
D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D015534:Trans-Activators; D007371:Interferon-gamma; D012260:Ribonucleases