Synthetic alpha-mannosyl ceramide as a potent stimulant for an NKT cell repertoire bearing the invariant Valpha19-Jalpha26 TCR alpha chain.
A NKT cell repertoire is characterized by the expression of the Valpha19-Jalpha26 invariant TCR alpha chain (Valpha19 NKT cell). This repertoire, as well as a well-established Valpha14-Jalpha281 invariant TCR alpha(+) NKT cell subset (Valpha14 NKT cell), has been suggested to have important roles in the regulation of the immune system and, thus, is a major therapeutic target. Here, we attempted to find specific antigens for Valpha19 NKT cells. Valpha19 as well as Valpha14 NKT cells exhibited reactivity to alpha-galactosyl ceramide (alpha-GalCer). Thus, a series of monoglycosyl ceramides with an axially oriented glycosidic linkage between the sugar and ceramide moiety were synthesized and their antigenicity to Valpha19 NKT cells was determined by measuring their immune responses in culture with glycolipids. Comprehensive examinations revealed substantial antigenic activity for Valpha19 NKT cells by alpha-mannosyl ceramide.
Developmental Immunology Unit, Mitsubishi Kagaku Institute of Life Sciences, Tokyo 194-8511, Japan.
Naoki
N
Okamoto
Osamu
O
Kanie
Yi-Ying
YY
Huang
Rei
R
Fujii
Hiroko
H
Watanabe
Michio
M
Shimamura
D000818:Animals; D000941:Antigens / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D002518:Ceramides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D005688:Galactosamine / Q000737:chemistry; D005944:Glucosamine / Q000737:chemistry; D020723:Glucuronic Acid / Q000737:chemistry; D006017:Glycolipids / Q000276:immunology; D006028:Glycosphingolipids / Q000138:chemical synthesis / Q000737:chemistry; D006031:Glycosylation; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000166:cytology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008358:Mannose / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*
D000941:Antigens; D000944:Antigens, Differentiation, B-Lymphocyte; D002518:Ceramides; D006017:Glycolipids; D006028:Glycosphingolipids; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta; C045084:invariant chain; D005688:Galactosamine; D020723:Glucuronic Acid; D005944:Glucosamine; D008358:Mannose