Abstract
Class II major histocompatibility complex (MHC) genes and the invariant (11) gene are inducible by interferonγ (IFNγ) but not by interferon-α and interferon-β. The promoter regions of these genes contain three regulatory elements that mediate constitutive and IFNγ-induced expressions; however, none of the DNA-binding proteins that interact with these elements are regulated by IFNγ- Recently, a gene coding for a transactivator (CIITA) of class II MHC genes that complements a HLADR-negative immunodeficiency has been isolated. Using one IFNγ mutant cell line (G3A) that is selectively defective in HLA-DR and li induction, four lines of evidence are presented to show that CIITA mediates the IFNγ induction of HLA-DR and Ii genes. Analysis of another mutant line, G1B, indicates that the lack of DRA and li gene Induction by IFNγ is correlated with the lack of RFX DNA binding activity, thus providing the link between RFX and an IFNγ response.
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