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

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, Rachel M. Ndonye, Amy R. Howell, Weiming Yuan, Peter Cresswell, Young tae Chang, Petr A. Illarionov, Gurdyal S. Besra, Steven A. Porcelli

Research output: Contribution to journalArticle

134 Scopus citations

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 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 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 anti-inflammatory activities of NKT cells.

Original languageEnglish (US)
Pages (from-to)888-898
Number of pages11
JournalImmunity
Volume30
Issue number6
DOIs
StatePublished - Jun 19 2009

Keywords

  • CELLIMMUNO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Im, J. S., Arora, P., Bricard, G., Molano, A., Venkataswamy, M. M., Baine, I., Jerud, E. S., Goldberg, M. F., Baena, A., Yu, K. O. A., Ndonye, R. M., Howell, A. R., Yuan, W., Cresswell, P., Chang, Y. T., Illarionov, P. A., Besra, G. S., & Porcelli, S. A. (2009). Kinetics and Cellular Site of Glycolipid Loading Control the Outcome of Natural Killer T Cell Activation. Immunity, 30(6), 888-898. https://doi.org/10.1016/j.immuni.2009.03.022