title: The 3-Deoxy Analogue of α-GalCer: Disclosing the Role of the 4-Hydroxyl Group for CD1d-Mediated NKT Cell Activation.
abstract: KRN7000, or α-GalCer, is a potent agonist for natural killer T (NKT) cells. The 3-hydroxyl group of its phytosphingosine moiety is important for activating NKT cells, whereas its 4-hydroxyl group is perceived to be less crucial. To experimentally determine the role of the 4-hydroxyl group, we synthesized the 3-deoxy analogue of α-GalCer. It was found that 3-deoxy-α-GalCer induced potent cytokine responses from NKT cells, comparable to those of both α-GalCer and 4-deoxy-α-GalCer. This result and our docking studies suggest that the effects of an absence of the 3-hydroxyl group are compensated by the presence of a hydroxyl group at the C-4 position. Thus, we conclude that the 4-hydroxyl group of α-GalCer is as important to the mechanism of action as the 3-hydroxyl group and that the two hydroxyl groups could play individual and cooperative roles in orienting the glycolipid into the proper position in CD1d to be recognized by the T cell receptor of NKT cells.
authors.affiliation: College of Pharmacy, Seoul National University , San 56-1, Shilim, Kwanak, Seoul 151-742, Korea.
authors.forename: Dong Jae
authors.initials: DJ
authors.lastname: Baek
authors.affiliation: College of Pharmacy, Seoul National University , San 56-1, Shilim, Kwanak, Seoul 151-742, Korea.
authors.forename: Jeong-Hwan
authors.initials: JH
authors.lastname: Seo
authors.affiliation: College of Pharmacy, Seoul National University , San 56-1, Shilim, Kwanak, Seoul 151-742, Korea.
authors.forename: Chaemin
authors.initials: C
authors.lastname: Lim
authors.affiliation: College of Pharmacy, Seoul National University , San 56-1, Shilim, Kwanak, Seoul 151-742, Korea.
authors.forename: Jae Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: College of Medicine, Seoul National University , 28 Yongon, Chongno, Seoul 110-799, Korea.
authors.forename: Doo Hyun
authors.initials: DH
authors.lastname: Chung
authors.affiliation: College of Pharmacy, Chonnam National University , Yongbong, Buk, Kwangju 500-757, Korea.
authors.forename: Won-Jea
authors.initials: WJ
authors.lastname: Cho
authors.affiliation: College of Pharmacy, Seoul National University , San 56-1, Shilim, Kwanak, Seoul 151-742, Korea.
authors.forename: Chang-Yuil
authors.initials: CY
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Seoul National University , San 56-1, Shilim, Kwanak, Seoul 151-742, Korea.
authors.forename: Sanghee
authors.initials: S
authors.lastname: Kim
keywords: CD1d; T cell receptor; deoxy analogues; glycolipid; natural killer T cells; α-GalCer