DYNAMIC MICRODOMAINS · Dynamics of DC-SIGN microdomains mediating recognition and uptake of viruses by dendritic cells
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2005-09-01 → 2006-08-31
- EU contribution
- €0
- Participants
- 1
- Scheme
- EIF
Lines connect the coordinator with its partners. CORDIS does not always give exact coordinates for projects before 2014. These points are placed at city or country level.
Project objective
Dendritic cells (DCs) are the sentinels of the immune system. They are bone marrow-derived, phagocytic cells, located in tissues to patrol for foreign antigens and present them to T cells. DC-SIGN is a DC-specific C-type lectin involved in adhesion and in pathogen-recognition, interacting with carbohydrate structures in a Ca2+-dependent manner. Life-threatening viruses like HIV-1, Ebola, and Hepatitis C virus are recognized by DC-SIGN. By high-resolution electron microscopy (EM), the applicant showed that o n DC cell membrane DC-SIGN can exist in two forms: randomly distributed or in submicron-sized (200 nm diameter) microdomains. These microdomains were shown to reside in lipid rafts and to be required for efficient binding and uptake of virus. How DC-SIGN m icrodomains are formed is largely unknown. The aim of this proposal is to follow the dynamics of DC-SIGN microdomains in living cells with high spatial and temporal resolution. Two aspects will be investigated: formation and stability of DC-SIGN microdomai ns as well as microdomain-mediated internalization and routing of virus-like particles. Fluorescence Resonance Energy Transfer (FRET) is a powerful tool for imaging molecular activities of suitably labeled DC-SIGN molecules in living cells. Ligand-coated h ighly-photostable Quantum Dots are excellent fluorescent probes for monitoring endocytosis and vesicular trafficking mediated by DC-SIGN micro-domains. Currently, DCs are manipulated ex vivo for the development of anti-tumour and anti-virus therapies. Therefore, this project will provide relevant information for important health-care areas, such asi) development of C-type lectin-based vaccines against invading pathogens; ii) study of antigen-routing mechanisms in DC cross-presentation; and iii) development o f C-type lectin-based targeting of DCs in anti-tumour strategies.
Original text from CORDIS.
Participants
- MAX PLANCK INSTITUTE FOR BIOPHYSICAL CHEMISTRYCoordinatorCity levelGermany
Links
Data: CORDIS, © European Union