1. Scavenger receptors target glycolipids for natural killer T cell activation
- Author
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Freigang, Stefan, Landais, Elise, Zadorozhny, Victoria, Kain, Lisa, Yoshida, Kenji, Liu, Yang, Deng, Shenglou, Palinski, Wulf, Savage, Paul B., Bendelac, Albert, and Teyton, Luc
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T cells -- Physiological aspects ,Blood lipoproteins -- Properties ,Proteolipids -- Properties ,Antigens -- Properties ,Lipoproteins -- Properties ,Glycolipids -- Properties ,Health care industry - 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 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 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 αGalCer and Sphingomonas glycolipids. Moreover, in vivo NKT cell responses, i.e., cytokine production, proliferation, and NKT cell help for adaptive [CD4.sup.+] and [CD8.sup.+] T cells, required the uptake of αGalCer 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., Introduction The efficacy of current vaccines depends on adjuvants, microbial products that activate the innate immune system by triggering pattern recognition receptors (PRRs), such as TLRs or NOD-like receptors (NLRs) [...]
- Published
- 2012
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