Structural reorganization of the antigen-binding groove of human CD1b for presentation of mycobacterial sulfoglycolipids

Garcia-Alles, L. F. and Collmann, A. and Versluis, C. and Lindner, B. and Guiard, J. and Maveyraud, L. and Huc, E. and Im, J. S. and Sansano, S. and Brando, T. and Julien, S. and Prandi, J. and Gilleron, M. and Porcelli, S. A. and de la Salle, H. and Heck, A. J. and Mori, L. and Puzo, G. and Mourey, L. and De Libero, G.. (2011) Structural reorganization of the antigen-binding groove of human CD1b for presentation of mycobacterial sulfoglycolipids. Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, H. 43. pp. 17755-17760.

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Official URL: http://edoc.unibas.ch/dok/A6338656

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The mechanisms permitting nonpolymorphic CD1 molecules to present lipid antigens that differ considerably in polar head and aliphatic tails remain elusive. It is also unclear why hydrophobic motifs in the aliphatic tails of some antigens, which presumably embed inside CD1 pockets, contribute to determinants for T-cell recognition. The 1.9-A crystal structure of an active complex of CD1b and a mycobacterial diacylsulfoglycolipid presented here provides some clues. Upon antigen binding, endogenous spacers of CD1b, which consist of a mixture of diradylglycerols, moved considerably within the lipid-binding groove. Spacer displacement was accompanied by F' pocket closure and an extensive rearrangement of residues exposed to T-cell receptors. Such structural reorganization resulted in reduction of the A' pocket capacity and led to incomplete embedding of the methyl-ramified portion of the phthioceranoyl chain of the antigen, explaining why such hydrophobic motifs are critical for T-cell receptor recognition. Mutagenesis experiments supported the functional importance of the observed structural alterations for T-cell stimulation. Overall, our data delineate a complex molecular mechanism combining spacer repositioning and ligand-induced conformational changes that, together with pocket intricacy, endows CD1b with the required molecular plasticity to present a broad range of structurally diverse antigens.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Experimental Immunology (De Libero)
UniBasel Contributors:De Libero, Gennaro
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:National Academy of Sciences
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:10 Apr 2015 09:13
Deposited On:10 Apr 2015 09:13

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