title: Role for lysosomal phospholipase A2 in iNKT cell-mediated CD1d recognition.
abstract: Invariant natural killer T (iNKT) cells recognize self lipid antigens presented by CD1d molecules. The nature of the self-antigens involved in the development and maturation of iNKT cells is poorly defined. Lysophospholipids are self-antigens presented by CD1d that are generated through the action of phospholipases A1 and A2. Lysosomal phospholipase A2 (LPLA2, group XV phospholipase A2) resides in the endocytic system, the main site where CD1d antigen acquisition occurs, suggesting that it could be particularly important in CD1d function. We find that Lpla2(-/-) mice show a decrease in iNKT cell numbers that is neither the result of a general effect on the development of lymphocyte populations nor of effects on CD1d expression. However, endogenous lipid antigen presentation by CD1d is reduced in the absence of LPLA2. Our data suggest that LPLA2 plays a role in the generation of CD1d complexes with thymic lipids required for the normal selection and maturation of iNKT cells.
authors.affiliation: Department of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520-8011, USA.
authors.forename: Crina
authors.initials: C
authors.lastname: Paduraru
authors.forename: Jelena S
authors.initials: JS
authors.lastname: Bezbradica
authors.forename: Amit
authors.initials: A
authors.lastname: Kunte
authors.forename: Robert
authors.initials: R
authors.lastname: Kelly
authors.forename: James A
authors.initials: JA
authors.lastname: Shayman
authors.forename: Natacha
authors.initials: N
authors.lastname: Veerapen
authors.forename: Liam R
authors.initials: LR
authors.lastname: Cox
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.forename: Peter
authors.initials: P
authors.lastname: Cresswell
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000276:immunology*; D000818:Animals; D017951:Antigen Presentation / Q000502:physiology*; D000941:Antigens / Q000235:genetics / Q000276:immunology; D055610:Antigens, CD1d / Q000235:genetics / Q000276:immunology*; D018655:Lymphocyte Count; D008247:Lysosomes / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology*; D054467:Phospholipases A2 / Q000235:genetics / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
chemical_list: D000941:Antigens; D055610:Antigens, CD1d; C526879:Cd1d1 protein, mouse; D000217:Acyltransferases; D054467:Phospholipases A2; C401297:phospholipase A2, group XV