Objective
Cytomegalovirus (CMV) is a ubiquitous herpesvirus, latently persisting in the majority of the adult population worldwide. In these hosts, CMV-specific memory cells dominate the immune memory compartment. It follows that CMV-specific T-cells dominate the memory compartment of the majority of the human population worldwide.
I propose to define within this project the molecular mechanisms driving the inflation of CMV-specific T-cells. My central hypothesis is that expression levels of CMV peptides during latency, along with the avidity of T-cell receptors for peptide MHC complexes, define the amplitude of T-cell responses. A corollary hypothesis is that vigorous T-cell responses in CMV infection are defined by factors that drive CMV gene expression during latency, such as inflammatory stimuli.
This hypothesis will be verified in a model of in vivo CMV latency and immune monitoring. We will benefit from state-of-the-art inducible genetic systems, where recombinant mouse CMV will be deployed in transgenic mice. In latently infected mice, we will induce or suppress the expression of immunodominant CMV genes, and define downstream effects on T-cell response kinetics. In parallel, we will define the T-cell responses to high and low avidity peptides.
Understanding the mechanisms driving the strong T-cell response to CMV is of outstanding biological and clinical relevance. If strong T-cell responses may be redirected to target heterologous antigens of interest, CMV-based vaccine vectors might potentially allow the development of HIV or tumor vaccines. On the other hand, it is speculated that the control of latent CMV may overcommit the aging immune system and exhaust the T-cell repertoire. Given the CMV pervasiveness, discerning the mechanisms of its T-cell induction may define novel molecular targets for rejuvenation strategies. In either case, the proposed research has groundbreaking potential in the field of infection and immunity.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences biochemistry biomolecules
- medical and health sciences basic medicine immunology
- medical and health sciences health sciences infectious diseases RNA viruses HIV
- 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.
ERC-2010-StG_20091118
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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.
Host institution
38124 Braunschweig
Germany
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.