Abstract
alpha-GalCer is the first defined and most potent agonistic antigen of the T cell receptor of natural killer T cells. We have prepared a series of 1,2,3-triazole-containing alpha-GalCer analogues in which the lipid chain lengths have been incrementally varied. We found that this isosteric replacement of alpha-GalCer's amide moiety with triazole increases the IL-4 versus IFN-gamma bias of released cytokines. The stimulatory effect was influenced by the length of the attached chain. In particular, the long-chained triazole analogues have a comparable stimulatory effect on cytokine production as alpha-GalCer and exhibit a stronger Th2 cytokine response.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / chemical synthesis*
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Adjuvants, Immunologic / chemistry
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Adjuvants, Immunologic / pharmacology
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Animals
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Antigens, CD1 / chemistry
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Antigens, CD1d
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Cell Line, Tumor
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Coculture Techniques
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Galactosylceramides / chemical synthesis*
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Galactosylceramides / chemistry
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Galactosylceramides / pharmacology
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Humans
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Hybridomas
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Interferon-gamma / metabolism
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Interleukin-2 / metabolism
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Interleukin-4 / metabolism
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Mice
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Mice, Inbred C57BL
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Models, Molecular
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Rats
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Receptors, Antigen, T-Cell / agonists
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Spleen / cytology
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Structure-Activity Relationship
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Th2 Cells / immunology
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Triazoles / chemical synthesis*
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Triazoles / chemistry
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Triazoles / pharmacology
Substances
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Adjuvants, Immunologic
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Antigens, CD1
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Antigens, CD1d
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CD1D protein, human
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Galactosylceramides
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Interleukin-2
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Receptors, Antigen, T-Cell
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Triazoles
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Interleukin-4
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Interferon-gamma
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KRN 7000