Molecular mechanisms of LFA-1 signaling involved in the priming phase of cytotoxic T lymphocytes by different DC subtypes

• Antragstellerin: Dr. Susanne Stutte
• Fachliche Zuordnung: Immunologie
• Förderung: Förderung von 2010 bis 2013
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 171071687

T lymphocytes have an essential function in protecting the host against pathogens. Especially CD8+ T cells are important for the elimination of pathogens like viruses or intracellular bacteria. Both the early fundamental decision whether or not a cytotoxic T lymphocyte (CTL) response is induced and the subsequent fine-tuning depends on information exchange between CD8+ T cells and dendritic cells (DC) in the lymph node (LN). However, the character of this essential cellular dialogue is still poorly understood. The aim of this study is to explore at subcellular resolution how naïve CD8+ T cells interact with different DC subpopulations of different peripheral origin during each of the three temporal priming phases. The novel Multi-photon-intra-vital-microscopy (MP-IVM) approach will be applied to observe CD8+ T cell-DC interactions in situ in mouse popliteal LN. The T cell-DC interface will be explored using covalently tagged LFA-1 and Q-dot-conjugated peptide-antigen as reporter molecules for LFA-1 and MHC complex distribution. Chimeric intracellular signaling molecules linked to fluorescent proteins enable to correlate T cell behavior with downstream signals of T cell receptor activation. This novel approach will give insight into the biology of spatio-temporal T cell – DC interactions required for CD8+ T cell activation.

• DFG-Verfahren: Forschungsstipendien
• Internationaler Bezug: USA
• Gastgeber: Professor Dr. Ulrich von Andrian