Intracellular routing of exogenous antigen within dendritic cells during crosspresentation

• Applicant: Dr. Claudia S. Wagner
• Subject Area: Immunology
• Term: from 2008 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 71124589

The main objective of this project is to define the intracellular trafficking pathways of exogenous antigens that gain access to the endoplasmic reticulum (ER) in dendritic cells (DCs) and how different forms of antigen uptake determine intracellular routing. This will allow a better understanding of the cell biological mechanism of how DCs process exogenously acquired antigens for presentation on MHC class I molecules to T cells, a process termed cross-presentation. Specific aims: 1. To determine whether exogenous antigens reach the ER exclusively after uptake by macropinocytosis or even when internalized by phagocytosis 2. To dissect which vesicular pathways and compartments are involved in transporting exogenous antigens to the ER a) To explore if exogenous soluble antigens use a retrograde transport mechanism involving the Golgi apparatus, as has been observed for some bacterial toxins that gain access to the ER b) To identify which Rab proteins (a family of GTPases regulating membrane traffic) are involved in intracellular transport of exogenous antigens towards the ER. To establish which Rab effector molecules and proteins involved in membrane fusion (SNAREs) are connected to this particular pathway. 3. To compare the trafficking pathway of soluble antigens to pathways coupled to other forms of uptake, such as phagocytosis, and to investigate the potential role of Derlin-1 in cross-presentation.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Peter Cresswell