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

Research output: Contribution to journalArticle


  • 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
  • SA Porcelli

Colleges, School and Institutes


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