C43H80O10

Natural killer T cells (NKT cells), unlike conventional T cells, specifically recognize self lipid– or foreign lipid–based antigens bound to the monomorphic MHC class I–like molecule CD1d. NKT cells have been linked to microbial immunity, autoimmunity, allergy and cancer and, accordingly, they represent an important immunotherapeutic target with immense clinical potential. Type I NKT cells express a semi-invariant TCR that has an invariant α-chain and a restricted TCRβ repertoire (α-chain variable region 24–α-chain joining region 18 paired with β-chain variable region 11 (Vα24-Jα18-Vβ11) in humans, and Vα14-Jα18 paired with Vβ8, Vβ7 or Vβ2 in mice). Nevertheless, despite this restricted TCR repertoire, NKT cell TCRs bind an array of different CD1d-restricted lipid-based antigens, including phospholipids9, as well as α-linked and β-linked glycolipids. The α-glycosidic linkage that defines α-galactosylceramide (α-GalCer) and other bacteria-derived NKT cell agonists, including α-glycuronosylceramides and α-galactosyldiacylglycerols, is considered to represent a 'microbial signature', as glycolipid antigens in mammals are typically β-linked anomers. The structures of NKT cell TCRs in complex with many α-linked glycolipids have been determined, including CD1d–α-GalCer and variants thereof and α-galactosyldiacylglycerol. Although the NKT cell TCR has been shown to be relatively rigid, conformational adjustments in complexes of CD1d and α-linked antigen permit optimal engagement of NKT cell TCRs. That is, a conserved docking topology is observed whereby the NKT cell TCR shows a parallel docking mode above the F′ pocket of the CD1d antigen-binding cleft, whereas the α-linked glycosyl moiety 'sits' snug and flat against CD1d, making many direct specificity-governing contacts with the NKT cell TCR. 2-O-oleoyl-3-O-palmitoyl-1-O-alpha-D-galactosyl-sn-glycerol is a 2,3-diacyl-1-alpha-D-galactosyl-sn-glycerol in which the groups at the 2- and 3-positions are oleoyl and palmitoyl respectively. It has a role as an antigen.