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Scavenger receptors target glycolipids for natural killer T cell activation.

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 alpha -galactosylceramide ( alpha GalCer), is currently being evaluated in clinical trials, but little is known... Full description

Journal Title: The Journal of clinical investigation November 2012, Vol.122(11), pp.3943-3954
Main Author: Freigang, Stefan
Other Authors: Landais, Elise , Zadorozhny, Victoria , Kain, Lisa , Yoshida, Kenji , Liu, Yang , Deng, Shenglou , Palinski, Wulf , Savage, Paul B , Bendelac, Albert , Teyton, Luc
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1558-8238 ; DOI: 10.1172/JCI62267
Link: http://search.proquest.com/docview/1126581030/?pq-origsite=primo
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recordid: proquest1126581030
title: Scavenger receptors target glycolipids for natural killer T cell activation.
format: Article
creator:
  • Freigang, Stefan
  • Landais, Elise
  • Zadorozhny, Victoria
  • Kain, Lisa
  • Yoshida, Kenji
  • Liu, Yang
  • Deng, Shenglou
  • Palinski, Wulf
  • Savage, Paul B
  • Bendelac, Albert
  • Teyton, Luc
subjects:
  • Animals–Physiology
  • Antigen Presentation–Immunology
  • Antigens, Bacterial–Immunology
  • Antigens, Cd1d–Immunology
  • Cd4-Positive T-Lymphocytes–Immunology
  • Cd8-Positive T-Lymphocytes–Immunology
  • Cell Line–Immunology
  • Galactosylceramides–Physiology
  • Glycosphingolipids–Immunology
  • Lymphocyte Activation–Genetics
  • Mice–Immunology
  • Mice, Knockout–Immunology
  • Natural Killer T-Cells–Immunology
  • Receptors, Scavenger–Immunology
  • Sphingomonas–Immunology
  • Abridged
  • Antigens, Bacterial
  • Antigens, Cd1d
  • Cd1d1 Protein, Mouse
  • Galactosylceramides
ispartof: The Journal of clinical investigation, November 2012, Vol.122(11), pp.3943-3954
description: 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 alpha -galactosylceramide ( alpha 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 alpha GalCer and Sphingomonas glycolipids. Moreover, in vivo NKT cell responses, i.e., cytokine production, proliferation, and NKT cell help for adaptive CD4 super( +) and CD8 super( +) T cells, required the uptake of alpha 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.
language: eng
source:
identifier: E-ISSN: 1558-8238 ; DOI: 10.1172/JCI62267
fulltext: fulltext
issn:
  • 15588238
  • 1558-8238
url: Link


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titleScavenger receptors target glycolipids for natural killer T cell activation.
creatorFreigang, Stefan ; Landais, Elise ; Zadorozhny, Victoria ; Kain, Lisa ; Yoshida, Kenji ; Liu, Yang ; Deng, Shenglou ; Palinski, Wulf ; Savage, Paul B ; Bendelac, Albert ; Teyton, Luc
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identifierE-ISSN: 1558-8238 ; DOI: 10.1172/JCI62267
subjectAnimals–Physiology ; Antigen Presentation–Immunology ; Antigens, Bacterial–Immunology ; Antigens, Cd1d–Immunology ; Cd4-Positive T-Lymphocytes–Immunology ; Cd8-Positive T-Lymphocytes–Immunology ; Cell Line–Immunology ; Galactosylceramides–Physiology ; Glycosphingolipids–Immunology ; Lymphocyte Activation–Genetics ; Mice–Immunology ; Mice, Knockout–Immunology ; Natural Killer T-Cells–Immunology ; Receptors, Scavenger–Immunology ; Sphingomonas–Immunology ; Abridged ; Antigens, Bacterial ; Antigens, Cd1d ; Cd1d1 Protein, Mouse ; Galactosylceramides
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descriptionNKT 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 alpha -galactosylceramide ( alpha 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 alpha GalCer and Sphingomonas glycolipids. Moreover, in vivo NKT cell responses, i.e., cytokine production, proliferation, and NKT cell help for adaptive CD4 super( +) and CD8 super( +) T cells, required the uptake of alpha 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.
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authorFreigang, Stefan ; Landais, Elise ; Zadorozhny, Victoria ; Kain, Lisa ; Yoshida, Kenji ; Liu, Yang ; Deng, Shenglou ; Palinski, Wulf ; Savage, Paul B ; Bendelac, Albert ; Teyton, Luc
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