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Modulation of CD1d-restricted NKT cell responses by using N-acyl variants of alpha-galactosylceramides.

ABSTRACT: A form of alpha-galactosylceramide, KRN7000, activates CD1d-restricted Valpha14-invariant (Valpha14i) natural killer (NK) T cells and initiates multiple downstream immune reactions. We report that substituting the C26:0 N-acyl chain of KRN7000 with shorter, unsaturated fatty acids modifies the outcome of Valpha14i NKT cell activation. One analogue containing a diunsaturated C20 fatty acid (C20:2) potently induced a T helper type 2-biased cytokine response, with diminished IFN-gamma production and reduced Valpha14i NKT cell expansion. C20:2 also exhibited less stringent requirements for loading onto CD1d than KRN7000, suggesting a mechanism for the immunomodulatory properties of this lipid. The differential cellular response elicited by this class of Valpha14i NKT cell agonists may prove to be useful in immunotherapeutic applications.

SUBMITTER: Yu KO 

PROVIDER: S-EPMC552918 | biostudies-literature | 2005 Mar

REPOSITORIES: biostudies-literature

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Modulation of CD1d-restricted NKT cell responses by using N-acyl variants of alpha-galactosylceramides.

Yu Karl O A KO   Im Jin S JS   Molano Alberto A   Dutronc Yves Y   Illarionov Petr A PA   Forestier Claire C   Fujiwara Nagatoshi N   Arias Isa I   Miyake Sachiko S   Yamamura Takashi T   Chang Young-Tae YT   Besra Gurdyal S GS   Porcelli Steven A SA  

Proceedings of the National Academy of Sciences of the United States of America 20050218 9

A form of alpha-galactosylceramide, KRN7000, activates CD1d-restricted Valpha14-invariant (Valpha14i) natural killer (NK) T cells and initiates multiple downstream immune reactions. We report that substituting the C26:0 N-acyl chain of KRN7000 with shorter, unsaturated fatty acids modifies the outcome of Valpha14i NKT cell activation. One analogue containing a diunsaturated C20 fatty acid (C20:2) potently induced a T helper type 2-biased cytokine response, with diminished IFN-gamma production an  ...[more]

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