title: Fatty acyl structures of mycobacterium tuberculosis sulfoglycolipid govern T cell response.
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.
authors.affiliation: Departement Mécanismes Moléculaires des Infections Mycobactériennes, Centre National de la Recherche Scientifique, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Guiard
authors.forename: Anthony
authors.initials: A
authors.lastname: Collmann
authors.forename: Luis Fernando
authors.initials: LF
authors.lastname: Garcia-Alles
authors.forename: Lionel
authors.initials: L
authors.lastname: Mourey
authors.forename: Thérèse
authors.initials: T
authors.lastname: Brando
authors.forename: Lucia
authors.initials: L
authors.lastname: Mori
authors.forename: Martine
authors.initials: M
authors.lastname: Gilleron
authors.forename: Jacques
authors.initials: J
authors.lastname: Prandi
authors.forename: Gennaro
authors.initials: G
authors.lastname: De Libero
authors.forename: Germain
authors.initials: G
authors.lastname: Puzo
mesh_terms: D000818:Animals; D018949:Antigens, CD1 / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells; D005227:Fatty Acids / Q000737:chemistry; D006017:Glycolipids / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000276:immunology*; D011485:Protein Binding; D013601:T-Lymphocytes / Q000276:immunology*; D032581:Tuberculosis Vaccines
chemical_list: D018949:Antigens, CD1; C419394:CD1b antigen; D005227:Fatty Acids; D006017:Glycolipids; D032581:Tuberculosis Vaccines; C011117:sulfoglycolipids