Inhibitor (IK) of IFN-gamma induced HLA class II antigens expression also inhibits HLA class II constitutive expression in the human Raji B cell line.
The expression of major histocompatibility complex (MHC) class II antigens is constitutive in professional antigen presenting cells (APCs) but can also be induced by interferon-gamma (IFN-gamma) on the majority of the non professional APCs (e.g. fibroblasts). We have recently characterised a new factor called IK which is an efficient inhibitor of IFN-gamma induction of MHC class II antigens expression. Here, we demonstrate a novel role for IK in MHC class II expression since over-expression of this protein by stable transfection into human B cells led to a total disappearance of constitutive MHC class II mRNA expression. The class II transactivator (CIITA) is necessary for both constitutive and IFN-gamma induced MHC class II expressions. Examination of CIITA mRNA in IK stably transfected clones revealed a marked reduction of CIITA mRNA transcription. Taken together these results demonstrate that the IK protein plays a key role in the constitutive expression of MHC class II antigens and that inhibition induced by IK is upstream of CIITA in this regulatory pathway.
Vedrenne
J
J
INSERM U 396, Institut Biomédical des Cordeliers, Paris, France.
Assier
E
E
Pereno
R
R
Bouzinba-Segard
H
H
Azzarone
B
B
Jasmin
C
C
Charron
D
D
Krief
P
P
D001402:B-Lymphocytes; D002451:Cell Compartmentation; D016207:Cytokines / Q000502:physiology*; D003593:Cytoplasm / Q000378:metabolism; D005786:Gene Expression Regulation; D005802:Genes, MHC Class II; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D009687:Nuclear Proteins; D012333:RNA, Messenger / Q000235:genetics; D015534:Trans-Activators / Q000502:physiology*
D016207:Cytokines; D006684:HLA-DR Antigens; C090444:IK protein, human; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D012333:RNA, Messenger; D015534:Trans-Activators