Objective
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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences microbiology bacteriology
- natural sciences biological sciences microbiology virology
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine immunology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2002-MOBILITY-7
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Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
IIF - Marie Curie actions-Incoming International Fellowships
Coordinator
CRÉTEIL
France
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