Bacterial glycolipids and analogs as antigens for CD1d-restricted NKT cells.
The CD1 family of proteins binds self and foreign glycolipids for presentation to CD1-restricted T cells. To identify previously uncharacterized active CD1 ligands, especially those of microbial origin, numerous glycolipids were synthesized and tested for their ability to stimulate mouse and human natural killer T (NKT) cells. They included analogs of the well known NKT cell agonist alpha-galactosyl ceramide (alpha-GalCer), bacterial glycolipids, and variations of the self-glycolipid, sulfatide. Bacterial glycolipids, alpha-galacturonosyl-ceramides from Sphingomonas wittichii, although structurally similar to alpha-GalCer, have significant differences in the sugar head group as well as the ceramide portion. The Sphingomonas glycosphingolipids (GSLs) and sulfatide variants were shown to activate human NKT cells as measured by IL-4 and IFN-gamma secretion. Moreover, CD1d-dimer staining revealed human NKT cell reactivity toward these GSLs and to the sulfatides in a fashion comparable with alpha-GalCer. Because alpha-GalCer is a marine-sponge-derived ligand, our study here shows that bacterium-derived antigens are also able to stimulate mouse and human NKT cells.
Wu
Douglass
D
Department of Chemistry and the Skaggs Institute of Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Xing
Guo-Wen
GW
Poles
Michael A
MA
Horowitz
Amir
A
Kinjo
Yuki
Y
Sullivan
Barbara
B
Bodmer-Narkevitch
Vera
V
Plettenburg
Oliver
O
Kronenberg
Mitchell
M
Tsuji
Moriya
M
Ho
David D
DD
Wong
Chi-Huey
CH
D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology*; D018949:Antigens, CD1 / Q000276:immunology*; D055610:Antigens, CD1d; D001419:Bacteria / Q000276:immunology*; D002460:Cell Line; D002518:Ceramides / Q000737:chemistry; D006017:Glycolipids / Q000737:chemistry / Q000276:immunology*; D006028:Glycosphingolipids / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D020578:Sphingomonas / Q000276:immunology*; D013110:Sphingosine / Q000737:chemistry; D013601:T-Lymphocytes / Q000276:immunology
D000942:Antigens, Bacterial; D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D002518:Ceramides; D006017:Glycolipids; D006028:Glycosphingolipids; D013110:Sphingosine