Fatty acyl structures of mycobacterium tuberculosis sulfoglycolipid govern T cell response.
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.
Guiard
Julie
J
Departement Mécanismes Moléculaires des Infections Mycobactériennes, Centre National de la Recherche Scientifique, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France.
Collmann
Anthony
A
Garcia-Alles
Luis Fernando
LF
Mourey
Lionel
L
Brando
Thérèse
T
Mori
Lucia
L
Gilleron
Martine
M
Prandi
Jacques
J
De Libero
Gennaro
G
Puzo
Germain
G
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
D018949:Antigens, CD1; C419394:CD1b antigen; D005227:Fatty Acids; D006017:Glycolipids; D032581:Tuberculosis Vaccines; C011117:sulfoglycolipids