Induction of promotive rather than suppressive immune responses from a novel NKT cell repertoire Valpha19 NKT cell with alpha-mannosyl ceramide analogues consisting of the immunosuppressant ISP-I as the sphingosine unit.
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 alpha-mannosyl ceramide (alpha-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 alpha-ManCer analogues induced immunopromotive responses from invariant Valpha19-Jalpha26 transgenic mouse lymphocytes more effectively than the original alpha-ManCer. Collectively, it is strongly suggested that the 2-substituted 2-aminopropane-1,3-diols and 2-aminoethanols mimic sphingosine in the alpha-ManCer analogues so that they potentially acquire specific antigenicity toward Valpha19 NKT cell, a novel NKT cell subset.
Developmental Immunology Unit, Mitsubishi Kagaku Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan. michio@libra.ls.m-kagaku.co.jp
Michio
M
Shimamura
Naoki
N
Okamoto
Yi-Ying
YY
Huang
Jouji
J
Yasuoka
Kenji
K
Morita
Akira
A
Nishiyama
Yuusuke
Y
Amano
Tadashi
T
Mishina
D000818:Animals; D002478:Cells, Cultured; D002518:Ceramides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D015394:Molecular Structure; D009005:Monosaccharides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013110:Sphingosine / Q000737:chemistry*; D013329:Structure-Activity Relationship; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology*
D002518:Ceramides; D005229:Fatty Acids, Monounsaturated; D007166:Immunosuppressive Agents; D009005:Monosaccharides; D013110:Sphingosine; C001996:thermozymocidin