Objective
An effective immune response relies on the helper T cell (TH) regulated development of high-affinity B cell memory. Follicular Helper T (TFH) cells are the critical regulators of the B cell response. Until recently, TFH cells were considered fully differentiated cells prone to apoptosis. However, we showed that protein vaccination selects locally effector TFH cells that become memory TFH cells and that remain in draining lymphoid tissue. Long-term cellular depots of antigen in the form of peptide-MHC complexes (pMHCII) and continued expression of the C-type lectin CD69 provide a mechanism for retaining TFH cells. Much is still to be learnt about the phenotype, function and ultimate fate of TFH cells. The relationship of effector TFH cells to other effector TH cell subsets and the mechanisms that control TFH cell differentiation are still uncovered. The genetic program imprinted in TFH cells by unique transcription factor(s), the role of cytokines or co-stimulatory signals and the impact of the inflammatory context in vivo in controlling TFH differentation will be assessed in the specific aim 1. Furthermore, unraveling the development and appropriate placement of memory TFH cells becomes an important issue. In specific aim 2, we will clarify the mechanism and role of memory TFH cell retention locally. First, we will assess the role of pMHCII depot by identifying which Antigen Presenting Cells (APC) express these depots. Next, we will confirm the importance of those APC in mice rendered deficient for this distinct population and test its physiological role. Finally, we will examine the role of CD69 as a potential retention mechanism in CD69-deficient mice. Over the course of these studies we will provide fundamental new insights into the mechanisms controlling adaptive immunity and help to define the best means to obtain long-lasting high-affinity B cell immunity to protein antigens with potentially high impact on the public health initiative of vaccine design.
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.
- medical and health sciences health sciences public health
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine immunology
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2009-RG
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Funding Scheme
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.
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.
Coordinator
75654 PARIS
France
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.