title: Peroxisome-derived lipids are self antigens that stimulate invariant natural killer T cells in the thymus.
abstract: The development and maturation of semi-invariant natural killer T cells (iNKT cells) rely on the recognition of self antigens presented by CD1d restriction molecules in thymus. The nature of the stimulatory thymic self lipids remains elusive. We isolated lipids from thymocytes and found that ether-bonded mono-alkyl glycerophosphates and the precursors and degradation products of plasmalogens stimulated iNKT cells. Synthetic analogs showed high potency in activating thymic and peripheral iNKT cells. Mice deficient in the peroxisomal enzyme glyceronephosphate O-acyltransferase (GNPAT), essential for the synthesis of ether lipids, had significant alteration of the thymic maturation of iNKT cells and fewer iNKT cells in both thymus and peripheral organs, which confirmed the role of ether-bonded lipids as iNKT cell antigens. Thus, peroxisome-derived lipids are nonredundant self antigens required for the generation of a full iNKT cell repertoire.
authors.affiliation: Experimental Immunology, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Federica
authors.initials: F
authors.lastname: Facciotti
authors.forename: Gundimeda S
authors.initials: GS
authors.lastname: Ramanjaneyulu
authors.forename: Marco
authors.initials: M
authors.lastname: Lepore
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Sansano
authors.forename: Marco
authors.initials: M
authors.lastname: Cavallari
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kistowska
authors.forename: Sonja
authors.initials: S
authors.lastname: Forss-Petter
authors.forename: Guanghui
authors.initials: G
authors.lastname: Ni
authors.forename: Alessia
authors.initials: A
authors.lastname: Colone
authors.forename: Amit
authors.initials: A
authors.lastname: Singhal
authors.forename: Johannes
authors.initials: J
authors.lastname: Berger
authors.forename: Chengfeng
authors.initials: C
authors.lastname: Xia
authors.forename: Lucia
authors.initials: L
authors.lastname: Mori
authors.forename: Gennaro
authors.initials: G
authors.lastname: De Libero
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D055610:Antigens, CD1d / Q000276:immunology / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008055:Lipids / Q000276:immunology* / Q000302:isolation & purification; D008246:Lysophospholipids / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D020675:Peroxisomes / Q000737:chemistry / Q000276:immunology*; D010714:Phosphatidylethanolamines / Q000276:immunology / Q000378:metabolism; D060168:Thymocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology* / Q000378:metabolism; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D055610:Antigens, CD1d; D000945:Antigens, Differentiation, T-Lymphocyte; D015847:Interleukin-4; D037181:Lectins, C-Type; D008055:Lipids; D008246:Lysophospholipids; D010714:Phosphatidylethanolamines; D000099192:CD69 Antigens; C008301:lysophosphatidylethanolamine