Bidirectional binding of invariant chain peptides to an MHC class II molecule

S. Günther, A. Schlundt, J. Sticht, Y. Roske, U. Heinemann, K.-H. Wiesmüller, G. Jung, K. Falk, O. Rötzschke, C. Freund – 2010

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.

Titel
Bidirectional binding of invariant chain peptides to an MHC class II molecule
Verfasser
S. Günther, A. Schlundt, J. Sticht, Y. Roske, U. Heinemann, K.-H. Wiesmüller, G. Jung, K. Falk, O. Rötzschke, C. Freund
Datum
2010
Kennung
10.1073/pnas.1014708107
Zitierweise
PNAS 2010, 107 (51), 22219-22224
Art
Text
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