title: Kinetics and cellular site of glycolipid loading control the outcome of natural killer T cell activation.
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.
authors.affiliation: Department of Microbiology and Immunology , Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Jin S
authors.initials: JS
authors.lastname: Im
authors.forename: Pooja
authors.initials: P
authors.lastname: Arora
authors.forename: Gabriel
authors.initials: G
authors.lastname: Bricard
authors.forename: Alberto
authors.initials: A
authors.lastname: Molano
authors.forename: Manjunatha M
authors.initials: MM
authors.lastname: Venkataswamy
authors.forename: Ian
authors.initials: I
authors.lastname: Baine
authors.forename: Elliot S
authors.initials: ES
authors.lastname: Jerud
authors.forename: Michael F
authors.initials: MF
authors.lastname: Goldberg
authors.forename: Andres
authors.initials: A
authors.lastname: Baena
authors.forename: Karl O A
authors.initials: KO
authors.lastname: Yu
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Ndonye
authors.forename: Amy R
authors.initials: AR
authors.lastname: Howell
authors.forename: Weiming
authors.initials: W
authors.lastname: Yuan
authors.forename: Peter
authors.initials: P
authors.lastname: Cresswell
authors.forename: Young-Tae
authors.initials: YT
authors.lastname: Chang
authors.forename: Petr A
authors.initials: PA
authors.lastname: Illarionov
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.forename: Steven A
authors.initials: SA
authors.lastname: Porcelli
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D055610:Antigens, CD1d / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D005699:Galactosylceramides / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D021962:Membrane Microdomains / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*
chemical_list: D055610:Antigens, CD1d; D016207:Cytokines; D005699:Galactosylceramides; C493154:alpha-galactosylceramide