Modulation of CD1d-restricted NKT cell responses by using <i>N-</i> acyl variants of α-galactosylceramides

Karl O. A. Yu(Albert Einstein College of Medicine), Jin S. Im(Albert Einstein College of Medicine), Alberto Molano(Albert Einstein College of Medicine), Yves Dutronc(Albert Einstein College of Medicine), Petr A. Illarionov(Albert Einstein College of Medicine), Claire Forestier(Albert Einstein College of Medicine), Nagatoshi Fujiwara(Albert Einstein College of Medicine), Isa Arias(Albert Einstein College of Medicine), Sachiko Miyake(Albert Einstein College of Medicine), Takashi Yamamura(Albert Einstein College of Medicine), Young‐Tae Chang(Albert Einstein College of Medicine), Gurdyal S. Besra(Albert Einstein College of Medicine), Steven A. Porcelli(Albert Einstein College of Medicine)
Proceedings of the National Academy of Sciences
February 18, 2005
10.1073/pnas.0407488102
Cited by 326Open Access
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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.

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