Molecular analysis of G1B and G3A IFN gamma mutants reveals that defects in CIITA or RFX result in defective class II MHC and Ii gene induction.
Class II major histocompatibility complex (MHC) genes and the invariant (Ii) gene are inducible by interferon-gamma (IFN gamma) but not by interferon-alpha and interferon-beta. The promoter regions of these genes contain three regulatory elements that mediate constitutive and IFN gamma-induced expressions; however, none of the DNA-binding proteins that interact with these elements are regulated by IFN gamma. Recently, a gene coding for a transactivator (CIITA) of class II MHC genes that complements a HLA-DR-negative immunodeficiency has been isolated. Using one IFN gamma mutant cell line (G3A) that is selectively defective in HLA-DR and Ii induction, four lines of evidence are presented to show that CIITA mediates the IFN gamma induction of HLA-DR and Ii genes. Analysis of another mutant line, G1B, indicates that the lack of DRA and Ii gene induction by IFN gamma is correlated with the lack of RFX DNA binding activity, thus providing the link between RFX and an IFN gamma response.
Chin
K C
KC
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill 27599-7260, USA.
Mao
C
C
Skinner
C
C
Riley
J L
JL
Wright
K L
KL
Moreno
C S
CS
Stark
G R
GR
Boss
J M
JM
Ting
J P
JP
D000944:Antigens, Differentiation, B-Lymphocyte; D000951:Antigens, Neoplasm / Q000096:biosynthesis; D001483:Base Sequence; D002460:Cell Line; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D005802:Genes, MHC Class II; D006684:HLA-DR Antigens / Q000096:biosynthesis / Q000235:genetics; D059805:HLA-DR alpha-Chains; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D016372:RNA, Antisense / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid; D013997:Time Factors; D015534:Trans-Activators / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection
D000944:Antigens, Differentiation, B-Lymphocyte; D000951:Antigens, Neoplasm; D006684:HLA-DR Antigens; D059805:HLA-DR alpha-Chains; D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D016372:RNA, Antisense; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; C045084:invariant chain; D007371:Interferon-gamma