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Kinetics and cellular site of glycolipid loading control

By Jin S. Im, Pooja Arora, Gabriel Bricard, Alberto Molano, Manjunatha M. Venkataswamy, Ian Baine, Elliot S. Jerud, Michael F. Goldberg, Andres Baena, Karl O.A. Yu and Rachel M. Ndonye

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 α galactosylceramide (αGalCer) 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 αGalCer-CD1d complexes to visualize and quantitate glycolipid presentation, we found that Th2 cell-type cytokinebiasing ligands were characterized by rapid and direct loading of cell-surface CD1d proteins. Complexes formed by association of these Th2 cell-type cytokine-biasing αGalCer 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 antiinflammatory activities of NKT cells

Topics: QR180 Immunology
Publisher: Elsevier
Year: 2009
OAI identifier: oai:eprints.bham.ac.uk:242

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