Induction of HLA class II genes by IFN-gamma is transcriptional and requires a trans-acting protein.
HLA class II Ag are encoded by a family of related genes clustered in the HLA-D region of the MHC. The expression of this multi-gene family is highly regulated and this regulation is essential for the control of the immune response. Class II gene expression is constitutive in a limited number of cell types and can be induced by IFN-gamma in a number of class II negative cells. In this study, we have clarified two essential aspects of the regulation of HLA class II genes by IFN-gamma. 1) The induction mechanism operates at the level of transcription and there is a long lag phase in the signal transduction process. 2) The induction of class II genes requires the de novo synthesis of a new protein(s). On this basis, we propose that IFN-gamma regulates the transcription of HLA class II genes via the de novo synthesis of a trans-acting activator protein.
Amaldi
I
I
Department of Microbiology, University of Geneva Medical School, Switzerland.
Reith
W
W
Berte
C
C
Mach
B
B
D000944:Antigens, Differentiation, B-Lymphocyte; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects*; D005802:Genes, MHC Class II / Q000187:drug effects*; D006684:HLA-DR Antigens / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D012516:Osteosarcoma / Q000235:genetics; D014176:Protein Biosynthesis; D014157:Transcription Factors / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*
D000944:Antigens, Differentiation, B-Lymphocyte; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D014157:Transcription Factors; C045084:invariant chain; D007371:Interferon-gamma