Objective
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 Most interestingly, unpublished work from the laboratory of G.J. Haemmerling has evidenced the subdivision of CLIP into 2 functionally distinct portions.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.
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.
- natural sciences biological sciences biochemistry biomolecules
- natural sciences biological sciences genetics mutation
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Coordinator
69009 Heidelberg
Germany
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