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Immunity. 2009 Jun 19;30(6):888-98. doi: 10.1016/j.immuni.2009.03.022.

Kinetics and cellular site of glycolipid loading control the outcome of natural killer T cell activation.

Author information

1
Department of Microbiology and Immunology , Albert Einstein College of Medicine, Bronx, NY 10461, USA.

Abstract

CD1d-restricted natural killer T cells (NKT cells) possess a wide range of effector and regulatory activities that are related to their ability to secrete both T helper 1 (Th1) cell- and Th2 cell-type cytokines. We analyzed presentation of NKT cell activating alpha galactosylceramide (alphaGalCer) analogs that give predominantly Th2 cell-type cytokine responses to determine how ligand structure controls the outcome of NKT cell activation. Using a monoclonal antibody specific for alphaGalCer-CD1d complexes to visualize and quantitate glycolipid presentation, we found that Th2 cell-type cytokine-biasing ligands were characterized by rapid and direct loading of cell-surface CD1d proteins. Complexes formed by association of these Th2 cell-type cytokine-biasing alphaGalCer analogs with CD1d showed a distinctive exclusion from ganglioside-enriched, detergent-resistant plasma membrane microdomains of antigen-presenting cells. These findings help to explain how subtle alterations in glycolipid ligand structure can control the balance of proinflammatory and anti-inflammatory activities of NKT cells.

PMID:
19538930
PMCID:
PMC2719696
DOI:
10.1016/j.immuni.2009.03.022
[Indexed for MEDLINE]
Free PMC Article

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