Bidirectional binding of invariant chain peptides to an MHC class II molecule.
Proc Natl Acad Sci U S A
; 107(51): 22219-24, 2010 Dec 21.
Article
in En
| MEDLINE
| ID: mdl-21115828
ABSTRACT
T-cell recognition of peptides bound to MHC class II (MHCII) molecules is a central event in cell-mediated adaptive immunity. The current paradigm holds that prebound class II-associated invariant chain peptides (CLIP) and all subsequent antigens maintain a canonical orientation in the MHCII binding groove. Here we provide evidence for MHCII-bound CLIP inversion. NMR spectroscopy demonstrates that the interconversion from the canonical to the inverse alignment is a dynamic process, and X-ray crystallography shows that conserved MHC residues form a hydrogen bond network with the peptide backbone in both orientations. The natural catalyst HLA-DM accelerates peptide reorientation and the exchange of either canonically or inversely bound CLIP against antigenic peptide. Thus, noncanonical MHC-CLIP displays the hallmarks of a structurally and functionally intact antigen-presenting complex.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antigens, Differentiation, B-Lymphocyte
/
Histocompatibility Antigens Class II
/
HLA-DR1 Antigen
Limits:
Humans
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2010
Document type:
Article
Affiliation country:
Germany