Role of CD8+ dendritic cells in antigen (cross-) presentation and cytotoxic immunity of the mouse and the human

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In the immune system, antigen is taken up and processed by “dendritic cells” (DC), of which an important subgroup (20%) are CD8+DC. The exact contribution of CD8+DC to antigen (cross-)presentation, an absolutely central process for the establishment of immune tolerance and generation of immunity, could not be assessed to date due to the lack of suitable experimental systems. Numerous data, however, point to a pivotal role of these CD8+DC in the development of a cytotoxic response to viruses, intracellular bacteria, and certain tumors. Based on the identification of a surface receptor, which is exclusively expressed in cross-presenting CD8+DC, we will be able to genetically delete these DC in mice and thus define their role in the immune system at steady state (tolerance) and in infection (immunity). These studies will be accompanied by numerous approaches aimed at defining the function of CD8+ DC in various organs of wild type mice. At the same time, we will identify the human counterpart of murine CD8+DC. These human DC will be phenotypically characterized and functionally tested, in particular for their capacity to (cross-)present antigen to CD8+ T cells, which are the mainstay of the cytotoxic immune defense. These basic studies will provide information which may enable us in the future to develop fundamentally new types of vaccines optimized for the induction of cytotoxic T cells directed against viral diseases and tumors.