Induction of promotive rather than suppressive immune responses from a novel NKT cell repertoire Vα19 NKT cell with α-mannosyl ceramide analogues consisting of the immunosuppressant ISP-I as the sphingosine unit

• Published in: European journal of medicinal chemistry Vol. 41; no. 5; pp. 569 - 576
• Main Authors: Shimamura, Michio, Okamoto, Naoki, Huang, Yi-Ying, Yasuoka, Jouji, Morita, Kenji, Nishiyama, Akira, Amano, Yuusuke, Mishina, Tadashi
• Format: Journal Article
• Language: English
• Published: Elsevier Masson SAS 01.05.2006
• Subjects: glycosphingolipid; immunomodulation; NKT cell; immunomodulation; MNC; invariant Vα14-Jα18 TCR α; Vα19; glycosphingolipid; Vα14; invariant Vα19-Jα26 TCR α; NKT cell; α-ManCer
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2005.11.013

A 2-substituted 2-aminopropane-1,3-diol or 2-aminoethanol is the minimum structure required for the immunosuppressive activity of ISP-I, an antibiotic isolated from the culture broth of Isaria sinclairil. A series of α-mannosyl ceramide (α-ManCer) analogues was derived from 2-substituted 2-aminopropane-1,3-diols or 2-aminoethanols in place of sphingosine. The newly synthesized glycosides were evaluated for their effects on immune responses. In contrast to the immunosuppressive activity of the precursors, the α-ManCer analogues induced immunopromotive responses from invariant Vα19-Jα26 transgenic mouse lymphocytes more effectively than the original α-ManCer. Collectively, it is strongly suggested that the 2-substituted 2-aminopropane-1,3-diols and 2-aminoethanols mimic sphingosine in the α-ManCer analogues so that they potentially acquire specific antigenicity toward Vα19 NKT cell, a novel NKT cell subset. A series of α-mannosyl ceramide analogues derived from 2-substituted 2-aminopropane-1,3-diols or 2-aminoethanols, the minimum structure required for the immunosuppressive activity of an antibiotics ISP-I, in place of sphingosine was immunopromotive toward Vα19 NKT cell, a novel NKT cell subset.