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

Item Type:Article
Title:Bidirectional binding of invariant chain peptides to an MHC class II molecule
Creators Name:Guenther, S. and Schlundt, A. and Sticht, J. and Roske, Y. and Heinemann, U. and Wiesmueller, K.H. and Jung, G. and Falk, K. and Roetzschke, O. and Freund, C.
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.
Keywords:Bidirectional Binding, Antigen Presentation, Peptide Loading
Source:Proceedings of the National Academy of Sciences of the United States of America
ISSN:0027-8424
Publisher:National Academy of Sciences (U.S.A.)
Volume:107
Number:51
Page Range:22219-22224
Date:21 December 2010
Official Publication:https://doi.org/10.1073/pnas.1014708107
PubMed:View item in PubMed

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