Objetivo Cross presentation is the process by which professional antigen presenting cells (APCs) present phagocyted antigens in the context of MHC class I molecules (MHC I), to prime CD8+ T cells. Recent findings have revealed that this process takes place in a spe cialized, ER-phagosome mix compartment in the major APCs, like dendritic cells (DCs) and macrophages. This novel compartment was also shown to be self-sufficient for cross presentation. In this context, ER membranes are recruited to the forming phagosome and contribute to peptide translocation and loading on MHC I within phagosomes. Internalised antigens are partially degraded before translocation to the cytosol and processing by the proteasome. Processed peptides are then returned inside phagosome to be loaded on MHC I molecules. Peptide loaded MHC class I molecules then reach the plasma membrane where CD8+ T cells recognize them. Despite the evidences of ER contribution in phagocytosis process, the molecules responsible for ER-phagosome fusion remain unknown as well the origin of the MHC class I molecules involved in cross presentation is still unclear.Our aim for this proposal is to elucidate the components of the molecular machinery involved in ER-phagosome fusion and to analyse the trafficking of MHC I molecules during cross presentation. SNAREs and Rabs are two protein families involved in membrane trafficking and fusion. We have observed the presence of the ER SNARE Sec22 and the plasma membrane t-SNAREs syntaxin3, syntaxin4 and SNAP23, as well Rab1 and Rab2 on purified phagosomes from D1 dendritic cells. These data suggest that some of them could be involved in ER-phagosome fusion. We will directly address this possibility using both in vivo and in vitro approaches, such as silencing protein production utilizing siRNA, transfection assays, and an in vitro fusion assay between purified ER membranes and purified phagosomes. Ámbito científico natural sciencesbiological sciencesmicrobiologybacteriologynatural sciencesbiological sciencesmicrobiologyvirologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicineimmunology Palabras clave Cross-presentation ER-phagosome compartment MHC trafficking SNARE membrane fusion Programa(s) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Tema(s) MOBILITY-2.3 - Marie Curie Incoming International Fellowships (IIF) Convocatoria de propuestas FP6-2002-MOBILITY-7 Consulte otros proyectos de esta convocatoria Régimen de financiación IIF - Marie Curie actions-Incoming International Fellowships Coordinador INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE Aportación de la UE Sin datos Dirección 51, avenue du Maréchal de Lattre de Tassigny -Hopital Henri Mondor CRÉTEIL Francia Ver en el mapa Enlaces Sitio web Opens in new window Coste total Sin datos
