title: Lipids are required for the development of Brazil nut allergy: the role of mouse and human iNKT cells.
abstract: BACKGROUND
  Lipids are required for mice sensitization to Ber e 1, Brazil nut major allergen. Here, we characterized different lipid fractions extracted from Brazil nuts and the lipid-binding ability of Ber e 1. Further, we determined their in vivo ability to induce Ber-specific anaphylactic antibodies and the role of invariant natural killer T (iNKT) cells in this process.
  
  
  METHODS
  Wild-type (WT) and iNKT cell-deficient mice were sensitized with Ber e 1 and specific lipid fractions, and anaphylactic antibodies were measured by enzyme-linked immunosorbent assay (ELISA) and passive cutaneous anaphylaxis (PCA). The lipid-binding characteristic of Ber e 1 (Ber) was established by using fluorescent probes and (15) N-labeled NMR. In vitro production of IL-4 was determined in Ber/lipid C-stimulated mouse iNKT cells and human T-cell lines containing NKTs primed with CD1d+C1R transfectants by flow cytometry and ELISA, respectively.
  
  
  RESULTS
  Only one specific lipid fraction (lipid C), containing neutral and common phospholipids, induced Ber anaphylactic antibodies in mice. Ber e 1 has a lipid-binding site, and our results indicated an interaction between Ber e 1 and lipid C. iNKT-deficient mice produced lower levels of anaphylactic antibodies than WT mice. In vitro, Ber/lipid C-stimulated murine iNKT cells produced IL-4 but not IFN-gamma. Human T-cell lines derived from nut-allergic patients produced IL-4 to Ber/lipid C in a CD1d- and dose-dependent manner.
  
  
  CONCLUSIONS
  Lipid fraction C from Brazil nut presents an essential adjuvant activity to Ber e 1 sensitization, and iNKT cells play a critical role in the development of Brazil nut-allergic response.
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brasil. lmirotti@gmail.com
authors.forename: L
authors.initials: L
authors.lastname: Mirotti
authors.forename: E
authors.initials: E
authors.lastname: Florsheim
authors.forename: L
authors.initials: L
authors.lastname: Rundqvist
authors.forename: G
authors.initials: G
authors.lastname: Larsson
authors.forename: F
authors.initials: F
authors.lastname: Spinozzi
authors.forename: M
authors.initials: M
authors.lastname: Leite-de-Moraes
authors.forename: M
authors.initials: M
authors.lastname: Russo
authors.forename: M
authors.initials: M
authors.lastname: Alcocer
mesh_terms: D055516:2S Albumins, Plant / Q000737:chemistry / Q000276:immunology; D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D052179:Antigens, Plant / Q000737:chemistry / Q000276:immunology; D001665:Binding Sites; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008055:Lipids / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D055611:Natural Killer T-Cells / Q000276:immunology*; D021184:Nut Hypersensitivity / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding; D018418:Th2 Cells / Q000276:immunology; D055815:Young Adult
chemical_list: D055516:2S Albumins, Plant; D000485:Allergens; D000906:Antibodies; D052179:Antigens, Plant; D008055:Lipids; C103364:2S albumin, brazil nut