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Lipids are required for the development of Brazil nut allergy: the role of mouse and human iNKT cells
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
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2013 (English)In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 68, no 1, 74-83 p.Article in journal (Refereed) Published
Abstract [en]

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 15N-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.

Conclusion 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.

Place, publisher, year, edition, pages
Hoboken, NJ, USA: Wiley-Blackwell, 2013. Vol. 68, no 1, 74-83 p.
Keyword [en]
anaphylactic antibodies, food allergy, humans, lipids, NKT cells
National Category
Respiratory Medicine and Allergy Immunology in the medical area
URN: urn:nbn:se:umu:diva-63751DOI: 10.1111/all.12057ISI: 000311974500009OAI: diva2:585642
Available from: 2013-01-10 Created: 2013-01-07 Last updated: 2013-04-12Bibliographically approved
In thesis
1. Thermodynamical and structural properties of proteins and their role in food allergy
Open this publication in new window or tab >>Thermodynamical and structural properties of proteins and their role in food allergy
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Proteins are important building blocks of all living organisms. They are composed of a defined sequence of different amino acids, and fold into a specific three-dimensional, ordered structure. The three-dimensional structure largely determines the function of the protein, but protein function always requires motion. Small movements within the protein structure govern the functional properties, and this thesis aims to better understand these discrete protein movements. The motions within the protein structure are governed by thermodynamics, which therefore is useful to predict protein interactions.

Nuclear magnetic resonance (NMR) is a powerful tool to study proteins at atomic resolution. Therefore, NMR is the primary method used within this thesis, along with other biophysical techniques such as Fluorescence spectroscopy, Circular Dichroism spectroscopy and in silico modeling.

In paper I, NMR in combination with molecular engineering is used to show that the folding of the catalytical subdomains of the enzyme Adenylate kinase does not affect the core of the protein, and thus takes a first step to linking folding, thermodynamic stability and catalysis.

In paper II, the structure of the primary allergen from Brazil nut, Ber e 1, is presented along with biophysical measurements that help explain the allergenic potential of the protein.

Paper III describes the need for a specific Brazil nut lipid fraction needed to induce an allergenic response. NMR and fluorescence spectroscopy is used to show that there is a direct interaction between Ber e 1 and one or several components in the lipid fraction.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2013. 33 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1571
Protein folding, NMR, Food allergy, allergen, protein interactions
National Category
Biophysics Structural Biology Biochemistry and Molecular Biology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Medical Biochemistry
urn:nbn:se:umu:diva-68020 (URN)978-91-7459-613-7 (ISBN)
Public defence
2013-05-03, KB3A9, plan 3, KBC-huset, Umeå Universitet, Umeå, 09:00 (English)
Available from: 2013-04-12 Created: 2013-04-10 Last updated: 2013-04-12Bibliographically approved

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Rundqvist, LouiseLarsson, Göran
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