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Scavenger receptors target glycolipids for natural killer T cell activation.


ABSTRACT: NKT cells are innate-like T cells with powerful regulatory functions that are a promising target for immunotherapy. The efficacy of glycolipids, such as the prototypic NKT cell antagonist ?-galactosylceramide (?GalCer), is currently being evaluated in clinical trials, but little is known about factors that target lipid antigens for CD1d presentation and NKT cell activation in vivo. Lipid uptake via the LDL receptor (LDLR) has been shown for digalactosylceramide; however, whether this pathway contributes to CD1d presentation of other important NKT cell agonists remains unclear. We therefore investigated receptor-mediated uptake pathways for CD1d presentation using a panel of structurally diverse lipid antigens. We found that uptake via scavenger receptors was essential for the CD1d presentation of ?GalCer and Sphingomonas glycolipids. Moreover, in vivo NKT cell responses, i.e., cytokine production, proliferation, and NKT cell help for adaptive CD4+ and CD8+ T cells, required the uptake of ?GalCer via scavenger receptor A. Importantly, our data indicate that structural characteristics of glycolipids determine their receptor binding and direct individual lipids toward different uptake pathways. These results reveal an important contribution of scavenger receptors in the selection of lipids for CD1d presentation and identify structural motifs that may prove useful for therapeutic NKT cell vaccination.

SUBMITTER: Freigang S 

PROVIDER: S-EPMC3484437 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Scavenger receptors target glycolipids for natural killer T cell activation.

Freigang Stefan S   Landais Elise E   Zadorozhny Victoria V   Kain Lisa L   Yoshida Kenji K   Liu Yang Y   Deng Shenglou S   Palinski Wulf W   Savage Paul B PB   Bendelac Albert A   Teyton Luc L  

The Journal of clinical investigation 20121015 11


NKT cells are innate-like T cells with powerful regulatory functions that are a promising target for immunotherapy. The efficacy of glycolipids, such as the prototypic NKT cell antagonist α-galactosylceramide (αGalCer), is currently being evaluated in clinical trials, but little is known about factors that target lipid antigens for CD1d presentation and NKT cell activation in vivo. Lipid uptake via the LDL receptor (LDLR) has been shown for digalactosylceramide; however, whether this pathway con  ...[more]

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