Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • 100th Anniversary of Insulin's Discovery (Jan 2021)
    • Hypoxia-inducible factors in disease pathophysiology and therapeutics (Oct 2020)
    • Latency in Infectious Disease (Jul 2020)
    • Immunotherapy in Hematological Cancers (Apr 2020)
    • Big Data's Future in Medicine (Feb 2020)
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • View all review series ...
  • Viewpoint
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
Scavenger receptors target glycolipids for natural killer T cell activation
Stefan Freigang, … , Albert Bendelac, Luc Teyton
Stefan Freigang, … , Albert Bendelac, Luc Teyton
Published October 15, 2012
Citation Information: J Clin Invest. 2012;122(11):3943-3954. https://doi.org/10.1172/JCI62267.
View: Text | PDF
Research Article

Scavenger receptors target glycolipids for natural killer T cell activation

  • Text
  • PDF
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+ and CD8+ 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.

Authors

Stefan Freigang, Elise Landais, Victoria Zadorozhny, Lisa Kain, Kenji Yoshida, Yang Liu, Shenglou Deng, Wulf Palinski, Paul B. Savage, Albert Bendelac, Luc Teyton

×

Figure 1

SRs are required for CD1d presentation of αGalCer and of bacterial glycolipid antigen.

Options: View larger image (or click on image) Download as PowerPoint
SRs are required for CD1d presentation of αGalCer and of bacterial glyco...
(A–D) CD1d presentation of the indicated NKT cell agonists to the Vα14+ NKT cell hybridoma DN32.D3 by bone marrow–derived DCs in vitro. DCs were derived from receptor-deficient mice (black circles) lacking expression of either (A) Ldlr, (B) Sra, (C) Srb1, or (D) Cd36 or from the respective WT control mice (white circles, A–D). The dose-response curves for each lipid antigen were used to calculate the ΔEC50 for each of the uptake receptors. PBS-18, αGal(α1-2)GalCer; PBS-29, synthetic Sphingomonas αGluACer. Mean ± SEM values of triplicate determinations representative for 1 of at least 3 independent experiments are shown.
Follow JCI:
Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts