Kurzfassung

Dendritic Cells (DC) are the crucial antigen presenting cells for the induction of cytotoxic T cell (CTL) responses. To prime naïve CTL, DC need to undergo a differentiation and activation process that can be triggered by a variety of signals, that are hallmarks of pathogen presence and inflammation. In particular, direct recognition of microbial components through pathogen recognition receptors such as Toll Like Receptors leads to DC activation. However, recent research has suggested that in...Dendritic Cells (DC) are the crucial antigen presenting cells for the induction of cytotoxic T cell (CTL) responses. To prime naïve CTL, DC need to undergo a differentiation and activation process that can be triggered by a variety of signals, that are hallmarks of pathogen presence and inflammation. In particular, direct recognition of microbial components through pathogen recognition receptors such as Toll Like Receptors leads to DC activation. However, recent research has suggested that in addition to this direct recognition of pathogens by Dendritic cells, cooperation with other Cell types like plasmacytoid dendritic cells or T helper cells are required for fully-fledged DC activation. Type I Interferons and CD40-CD40 Ligand interactions have been implicated as mediators of such cooperations. However, the role of these interactions in DC activation and their contribution to CTL priming in vivo has been difficult to study due to the pleiotropic effects of the molecules involved. We will use a novel transgenic mouse model, which we have recently generated, to study the effect of these signals on the activation of antigen presenting DC isolated from any other functions of these molecules. This mouse model allows the inducible expression of viral CTL epitopes specifically on dendritic cells. We will cross these mice to mice deficient in receptors that have been implied in DC activating cellular interactions like Type I Interferon receptor and CD40 and generate mixed bone marrow chimeric mice in which the antigen presenting transgenic DC are the only relevant cells that cannot receive signals via these receptors. We will use this setup

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