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EditMHC SIGNED

How MHC-I editing complexes shape the hierarchical immune response

Total Cost €

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EC-Contrib. €

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Partnership

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 EditMHC project word cloud

Explore the words cloud of the EditMHC project. It provides you a very rough idea of what is the project "EditMHC" about.

diseases    proteasomal    immune    plc    inner    calreticulin    constitutes    mechanistic    peptides    consequently    holistic    erp57    scanned    central    stable    machinery    coordinated    guarantees    mhc    gain    presented    cell    proofreading    basis    membrane    dynamic    macromolecular    transporter    assemblies    architecture    epitopes    body    precisely    surveillance    molecules    single    triggered    sampling    cytotoxic    class    lymphocytes    translocation    strive    elucidate    tap1    pathogens    transport    released    reactions    degradation    heterodimer    cancerous    viral    malignant    risk    orchestrates    mechanisms    health    constantly    evasion    infected    chaperone    place    chaperones    quality    tap    network    encounters    unraveling    transformation    eliminate    principles    ultimately    er    human    immunity    tapasin    intracellular    insights    antigen    multiprotein    multitasking    histocompatibility    dynamics    complexes    loading    cellular    multisubunit    assembly    peptide    oxidoreductase    pave    onto    surface    cells    our    allomorphs    adaptive    editing    antigenic    myriads   

Project "EditMHC" data sheet

The following table provides information about the project.

Coordinator		 JOHANN WOLFGANG GOETHE-UNIVERSITATFRANKFURT AM MAIN 

Organization address
address: THEODOR W ADORNO PLATZ 1
city: FRANKFURT AM MAIN
postcode: 60323
website: www.uni-frankfurt.de

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.
 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.

# participants  country  role  EC contrib. [€] 
1    JOHANN WOLFGANG GOETHE-UNIVERSITATFRANKFURT AM MAIN DE (FRANKFURT AM MAIN) coordinator 2˙181˙250.00

Map

 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
List of publications.
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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