EditMHC SIGNED
How MHC-I editing complexes shape the hierarchical immune response
Total Cost €
0EC-Contrib. €
0Partnership
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0EditMHC project word cloud
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Project "EditMHC" data sheet
The following table provides information about the project.
| Coordinator |
JOHANN WOLFGANG GOETHE-UNIVERSITATFRANKFURT AM MAIN
Organization address contact info |
| Coordinator Country | Germany [DE] |
| Total cost | 2˙181˙250 € |
| EC max contribution | 2˙181˙250 € (100%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2017-ADG |
| Funding Scheme | ERC-ADG |
| Starting year | 2019 |
| Duration (year-month-day) | from 2019-01-01 to 2023-12-31 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | JOHANN WOLFGANG GOETHE-UNIVERSITATFRANKFURT AM MAIN | DE (FRANKFURT AM MAIN) | coordinator | 2˙181˙250.00 |
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Project 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.
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2019 |
Susanne Hofmann, Dovile Januliene, Ahmad R. Mehdipour, Christoph Thomas, Erich Stefan, Stefan Brüchert, Benedikt T. Kuhn, Eric R. Geertsma, Gerhard Hummer, Robert Tampé, Arne Moeller Conformation space of a heterodimeric ABC exporter under turnover conditions published pages: 580-583, ISSN: 0028-0836, DOI: 10.1038/s41586-019-1391-0 |
Nature 571/7766 | 2020-01-30 |
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