Structure-based discovery of glycolipids for CD1d-mediated NKT cell activation: tuning the adjuvant versus immunosuppression activity.
Introduction of an aromatic group into the fatty acyl chain of alpha-GalCer modulates the activity and selectivity of IFN-gamma/IL-4 secretion through CD1d-mediated activation of NKT cells. Compound 14-16 are more potent than alpha-Galcer and biased for IFN-gamma than for IL-4. These new glycolipids may find use as adjuvants or as antimetastatic agents.
Fujio
Masakazu
M
The Scripps Research Institute, La Jolla, California 92037, USA.
Wu
Douglass
D
Garcia-Navarro
Raquel
R
Ho
David D
DD
Tsuji
Moriya
M
Wong
Chi-Huey
CH
D000818:Animals; D018949:Antigens, CD1 / Q000737:chemistry / Q000378:metabolism*; D055610:Antigens, CD1d; D002460:Cell Line; D005699:Galactosylceramides / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007165:Immunosuppression Therapy; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D005699:Galactosylceramides