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

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• 作者：Michio Shimamura ; Naoki Okamoto ; Yi-Ying Huang ; Jouji Yasuoka ; Kenji Morita ; Akira Nishiyama ; Yuusuke Amano ; Tadashi Mishina
• 关键词：NKT cell ; immunomodulation ; glycosphingolipid
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2006
• 出版时间：May 2006
• 年：2006
• 卷：41
• 期：5
• 页码：569-576
• 全文大小：454 K

文摘

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.