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Zawartość zarchiwizowana w dniu 2024-05-07

Functional dissection of mhc class ii associated invariant chain

Cel



The invariant chain (Ii) binds nascent Major Histocompatibility Complex class II molecules (MHC-II) in the endoplasmic reticulum, and prevents peptide binding. Once transported into the endosomes, MHC-II become available for antigenic peptide loading after stepwise removal of Ii. The Ii derived CLIP peptides have received great attention lately because they are the last fragment of Ii to be removed and because they retain its capacity to inhibit peptide loading on MHC-II. CLIP release from MHC-II appears thus as the key step in the generation of functional antigenic peptide/MHC-II complexes. But, how CLIP mediates peptide inhibition and how it is removed remains unknown so far. Most interestingly, unpublished work from the laboratory of G.J. Haemmerling has evidenced the subdivision of CLIP into 2 functionally distinct portions. The N-terminal segment confers intrinsic properties to CLIP facilitating its own release in endosomal compartments, while the C-terminal half is sufficient for inhibition of peptide binding. It is now important to assess whether these findings, obtained with synthetic peptides, extend to the whole Ii in cellular systems. I therefore propose to study in vivo the functional effect of mutations in the CLIP region of the human Ii.
This project aims to define the CLIP inhibitory motif with respect to peptide binding to MHC-II as well as to establish the molecular bases of the contribution of CLIP to its own removal in endosomal compartments.

Dziedzina nauki (EuroSciVoc)

Program(-y)

Temat(-y)

Zaproszenie do składania wniosków

Brak dostępnych danych

System finansowania

RGI - Research grants (individual fellowships)

Koordynator

Stiftung Deutsches Krebsforschungszentrum
Wkład UE
Brak danych
Adres
280,Im Neuenheimer Feld
69009 Heidelberg
Niemcy
Koszt całkowity
Brak danych

Uczestnicy (1)