Kinetics and Cellular Site of Glycolipid Loading Control the Outcome of Natural Killer T Cell Activation

JS Im, P Arora, G Bricard, A Molano, MM Venkataswamy, I Baine, ES Jerud, MF Goldberg, A Baena, KOA Yu, RM Ndonye, AR Howell, W Yuan, P Cresswell, YT Chang, Petr Illarionov, Gurdyal Besra, SA Porcelli

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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.
Original languageEnglish
Pages (from-to)888-898
Number of pages11
Issue number6
Publication statusPublished - 1 Jun 2009


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