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Fatty acyl structures of mycobacterium tuberculosis sulfoglycolipid govern T cell response

Guiard, Julie and Collmann, Anthony and Garcia-Alles, Luis Fernando and Mourey, Lionel and Brando, Thérèse and Mori, Lucia and Gilleron, Martine and Prandi, Jacques and De Libero, Gennaro and Puzo, Germain. (2009) Fatty acyl structures of mycobacterium tuberculosis sulfoglycolipid govern T cell response. Journal of immunology : official journal of the American Association of Immunologists, Vol. 182. pp. 7030-7037.

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Official URL: http://edoc.unibas.ch/dok/A6003716

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Abstract

CD1b-restricted T lymphocytes recognize a large diversity of mycobacterial lipids, which differ in their hydrophilic heads and the structure of their acyl appendages. Both moieties participate in the antigenicity of lipid Ags, but the structural constraints governing binding to CD1b and generation of antigenic CD1b:lipid Ag complexes are still poorly understood. Here, we investigated the structural requirements conferring antigenicity to Mycobacterium tuberculosis sulfoglycolipid Ags using a combination of CD1b:lipid binding and T cell activation assays with both living dendritic cells and plate-bound recombinant soluble CD1b. Comparison of the antigenicity of a panel of synthetic analogs, sharing the same trehalose-sulfate polar head, but differing in the structure of their acyl tails, shows that the number of C-methyl substituents on the fatty acid, the configuration of the chiral centers, and the respective localization of the two different acyl chains on the sugar moiety govern TCR recognition and T lymphocyte activation. These studies have major implications for the design of sulfoglycolipid analogs with potential use as tuberculosis subunit vaccines.
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
Bibsysno:Link to catalogue
Publisher:American Assoc. of Immunologists
ISSN:0022-1767
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Feb 2013 08:46
Deposited On:01 Feb 2013 08:41

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