1. Kinetics and Cellular Site of Glycolipid Loading Control the Outcome of Natural Killer T Cell Activation
- Author
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Peter Cresswell, Young-Tae Chang, Pooja Arora, Steven A. Porcelli, Michael F. Goldberg, Weiming Yuan, Manjunatha M. Venkataswamy, Andres Baena, Jin S. Im, Rachel M. Ndonye, Petr A. Illarionov, Karl O.A. Yu, Elliot S. Jerud, Gabriel Bricard, Amy R. Howell, Gurdyal S. Besra, Ian Baine, and Alberto Molano
- Subjects
medicine.medical_treatment ,Immunology ,Cell ,Antigen-Presenting Cells ,chemical and pharmacologic phenomena ,Galactosylceramides ,Biology ,Lymphocyte Activation ,Article ,Proinflammatory cytokine ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Glycolipid ,Membrane Microdomains ,Th2 Cells ,medicine ,Immunology and Allergy ,Animals ,Humans ,Secretion ,Antigen-presenting cell ,MOLIMMUNO ,030304 developmental biology ,0303 health sciences ,Mice, Inbred BALB C ,hemic and immune systems ,Natural killer T cell ,Cell biology ,Mice, Inbred C57BL ,Kinetics ,Infectious Diseases ,medicine.anatomical_structure ,Cytokine ,Biochemistry ,CELLIMMUNO ,CD1D ,biology.protein ,Cytokines ,Natural Killer T-Cells ,Female ,Antigens, CD1d ,030215 immunology - 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.
- Published
- 2009