Modulation of CD1d-restricted NKT cell responses by using N-acyl variants of α-galactosylceramides
Proceedings of the National Academy of Sciences, 2005•National Acad Sciences
A form of α-galactosylceramide, KRN7000, activates CD1d-restricted Vα14-invariant (Vα14i)
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 Vα14i 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-γ production and reduced Vα14i NKT cell expansion. C20: 2 also exhibited …
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 Vα14i 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-γ production and reduced Vα14i NKT cell expansion. C20: 2 also exhibited …
A form of α-galactosylceramide, KRN7000, activates CD1d-restricted Vα14-invariant (Vα14i) 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 Vα14i 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-γ production and reduced Vα14i 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 Vα14i NKT cell agonists may prove to be useful in immunotherapeutic applications.
National Acad Sciences