CD83 is one of the best-known surface markers for mature dendritic cells (DC). As CD83 is specifically upregulated upon DC maturation, a highly cell type- and maturation status-specific gene regulation is hypothesized. To elucidate the regulation mechanisms of CD83 expression in human DC, ChIP-chip-microarray-, biocomputational-, reporter, CpG-methylation- and EMSA -analyses were performed. By these studies, a tripartite transcriptional activation complex composed of an upstream regulatory element, a minimal promoter and an enhancer was identified. Their specific arrangement and cooperation in trans, mediated by a complex framework of IRF- and NFkB-binding sites, has not been reported for any other gene so far. The characterization of the CD83 promoter complex not only allows a detailed look into the elaborate mechanisms of the immune response in general and the biology of DC in particular, but also exemplarily unfolds the cooperation of various promoter elements in a highly cell type- and status-specific immune cell related promoter. Thus, for the first time, a human mature DC-specific promoter is described that might become an important tool for transcriptional targeting of DC.