Major histocompatibility complex (MHC) class I-deficient cell lines were used to demonstrate that the MHC class II transactivator (CIITA) can induce surface expression of MHC class I molecules. CIITA induces the promoter of MHC class I heavy chain genes. The site alpha DNA element is the target for CIITA-induced transactivation of class I. In addition, interferon-gamma (IFNgamma)-induced MHC class I expression also requires an intact site alpha. The G3A cell line, which is defective in CIITA induction, does not induce MHC class I antigen and promoter in response to IFNgamma. Trans-dominant-negative forms of CIITA reduce class I MHC promoter function and surface antigen expression. Collectively, these data argue that CIITA has a role in class I MHC gene induction.

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CIITA is a master transactivator of the major histocompatibility complex class II genes, which are involved in antigen presentation. Defects in CIITA result in fatal immunodeficiencies. CIITA activation is also the control point for the induction of major histocompatibility complex class II and associated genes by interferon-␥, but CIITA does not bind directly to DNA. Expression of CIITA in G3A cells, which lack endogenous CIITA, followed by in vivo genomic footprinting, now reveals that CIITA is required for the assembly of transcription factor complexes on the promoters of this gene family, including DRA, Ii, and DMB. CIITAdependent promoter assembly occurs in interferon-␥-inducible cell types, but not in B lymphocytes. Dissection of the CIITA protein indicates that transactivation and promoter loading are inseparable and reveal a requirement for a GTP binding motif. These findings suggest that CIITA may be a new class of transactivator.

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