The highly complex pattern of expression of major histocompatibility complex class II (MHC-II) molecules determines both the immune repertoire during development and subsequently the triggering and the control of immune responses. These distinct functions result from cell type-restricted expression, developmental control and either constitutive or inducible expression of MHC-II genes, Yet, in these various situations, MHC-II gene expression is always under the control of a unique transactivator, CIITA. Here we show that the CIITA gene is controlled by several distinct promoters, two of which direct specific constitutive expression in dendritic cells and B lymphocytes respectively, while another mediates gamma-interferon-induced expression, Thus the cellular, temporal and functional diversity of MHC-II expression is ultimately controlled by differential activation of different promoters of a single transactivator gene, This provides novel experimental tools to dissect compartment-specific gain or loss of MHC-H function in vivo.