The major aim of the research group is the functional characterization of the human DC-specific CD83 promoter. The membrane-bound CD83 molecule is a 45 kDa glycoprotein expressed on the surface of mature DC and is to date one of the best known markers for human mature DC. Since CD83 is not expressed on immature DCs, its regulatory DNA region, the CD83 promoter, is of high interest in the context of a DC-media- ted vaccination strategy for the modulation of mature DC by the targeted in vivo gene expression of different therapeutic transgenes.
For this purpose, different immune-modulatory and therapeutic transgenes will be expressed in vivo (directly in patients) under the control of the cell type- and stadium specific CD83 promoter. Initially, the characterization of the human CD83 promoter was accomplished by a ChIP-chipTM Microarray analysis, by which, in addition to the minimal promoter, a short enhancer sequence was identified.
Further, bio-informatical analysis identified an additional promoter region which was shown to build a ternary promoter-complex together with the minimal promoter and the enhancer. Moreover, we have demonstrated that this ternary promoter-complex is not only highly inducible, but it is also cell type- and maturation specific. Finally, we have identified the transcription factors involved in this process.