Objective
Our body constantly encounters pathogens or malignant transformation. Consequently, the adaptive immune system is in place to eliminate infected or cancerous cells. Specific immune reactions are triggered by selected peptide epitopes presented on major histocompatibility complex class I (MHC-I) molecules, which are scanned by cytotoxic T lymphocytes.
Intracellular transport, loading, and editing of antigenic peptides onto MHC-I are coordinated by a highly dynamic multisubunit peptide-loading complex (PLC) in the ER membrane. This multitasking machinery orchestrates the translocation of proteasomal degradation products into the ER as well as the loading and proofreading of MHC-I molecules.
Sampling of myriads of different peptide/MHC-I allomorphs requires a precisely coordinated quality control network in a single macromolecular assembly, including the transporter associated with antigen processing TAP1/2, the MHC-I heterodimer, the oxidoreductase ERp57, and the ER chaperones tapasin and calreticulin. Proofreading by MHC-I editing complexes guarantees that only very stable peptide/MHC-I complexes are released to the cell surface.
This proposal aims to gain a holistic understanding of the PLC and MHC-I proofreading complexes, which are essential for cellular immunity. We strive to elucidate the mechanistic basis of the antigen translocation complex TAP as well as the MHC-I chaperone complexes within the PLC. This high-risk/high-gain project will define the inner working of the PLC, which constitutes the central machinery of immune surveillance in health and diseases. The results will provide detailed insights into the architecture and dynamics of the PLC and will ultimately pave the way for unraveling general principles of intracellular membrane-embedded multiprotein assemblies in the human body. Furthermore, we will deliver a detailed understanding of mechanisms at work in viral immune evasion.
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.
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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)
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.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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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.
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.
ERC-ADG - Advanced Grant
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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.
(opens in new window) ERC-2017-ADG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
60323 Frankfurt Am Main
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.