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ImmunoMachines

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Unraveling the Supramolecular Architecture of Molecular Machineries in Adaptive...

Unraveling the Supramolecular Architecture of Molecular Machineries in Adaptive Immunity To combat daily threats of pathogens and abnormal cells, the human organism features a sophisticated defense mechanism called the adaptive immune system. In broad terms, this intricate mechanism is triggered by specific peptide ep... ver más

31/12/2029

GUF

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

JOHANN WOLFGANG GOETHEUNIVERSITAET FRANKFURT... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2025-01-01

ERC-2023-ADG: ERC ADVANCED GRANTS Scope:Objectives

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Duración del proyecto: 59 meses Fecha Inicio: 2025-01-01
Fecha Fin: 2029-12-31

Líder del proyecto

JOHANN WOLFGANG GOETHEUNIVERSITAET FRANKFURT... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto To combat daily threats of pathogens and abnormal cells, the human organism features a sophisticated defense mechanism called the adaptive immune system. In broad terms, this intricate mechanism is triggered by specific peptide epitopes presented on molecules of the major histocompatibility complex class I (MHC I), which are scanned by cytotoxic T cells. Intracellular transport, loading, and cell-surface recognition of antigenic peptides on MHC I are orchestrated by machineries, the peptide-loading complex (PLC) and the T cell receptor (TCR) complex. The PLC is composed of multiple subunits, including the antigen translocation unit TAP, the MHC I heterodimer, and several chaperones ensuring that only stable peptide-MHC I molecules are released to the cell surface for decoding by TCR complexes. Ligand binding and the supramolecular organization of TCR complexes are translated into phosphorylation of conserved tyrosine-containing cytosolic sequence motifs that initiate downstream signaling cascades. Based on their incredible efficiency and selectivity, we hypothesize that the biogenesis of MHC I is highly processive and coupled via allosteric networking, and that antigen processing and recognition machineries are compartmentalized by a defined supramolecular organization. However, despite their fundamental importance, these architectural details of the PLC and the TCR, as well as the dynamic networking that is included in the quality control of the endoplasmic reticulum (ER) and receptor signaling processes, remain enigmatic due to their inherent dynamics, low abundance, and complexity.This ambitious proposal will contribute to a long-awaited holistic understanding of the machineries that shape the vertebrate adaptive immunity. The expected findings from this project will be groundbreaking in understanding the hidden processes of epitope selection and reception in human disease.

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