Modulation of CD1d-restricted NKT Cell Responses by Using N-acyl Variants of Alpha-galactosylceramides

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2005 Feb 22

PMID 15722411

Citations 159

Authors

Karl O A Yu

Jin S Im

Alberto Molano

Yves Dutronc

Petr A Illarionov

Claire Forestier

Nagatoshi Fujiwara

Isa Arias

Sachiko Miyake

Takashi Yamamura

Young-Tae Chang

Gurdyal S Besra

Steven A Porcelli

Affiliations

Soon will be listed here.

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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