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Structural studies of insect allergens

English title Structural studies of insect allergens
Applicant Markovic-Housley Zora
Number 116804
Funding scheme Project funding (Div. I-III)
Research institution Abteilung Strukturbiologie und Biophysik Biozentrum Universität Basel
Institution of higher education University of Basel - BS
Main discipline Biophysics
Start/End 01.04.2007 - 31.03.2013
Approved amount 197'000.00
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Keywords (6)

protein crystallography; insect allergens; hyaluronidase; serine proteases; bee venom; wasp venom

Lay Summary (English)

Lead
Lay summary
Stings from bees, wasps and fire ants, the most common stinging insects of the order Hymenoptera, can cause severe (IgE)-mediated allergic reactions (type I hypersensitivity reaction). It has been estimated that up to 3\% of the general population have a history of systemic anaphylactic reactions to insect stings. Specific immunotherapy (SIT) with natural venom constituents remains the preferred and most effective treatment of insect venom allergy but is not without danger: 20--40\% of patients hyposensitized with bee venom extracts develop allergic side effects. Given the suddenness of the sting induced allergic reactions, which occasionally may be fatal, a better tolerated and effective SIT for insect venom allergy is urgently needed. Since the antigen-antibody (Ag-Ab) interactions are critical for triggering of allergic responses, the structures of the antigens and antigen/antibody complexes are essential for the identification of the allergen's epitopes which are recognised by IgE antibodies. The knowledge of the IgE-binding epitopes would enable the development of an improved and safer allergen specific immunotherapy (SIT).The objective of this proposal is to use X-ray crystallography to determine (i) the B-cell epitope(s) of bee venom hyaluronidase in complex with specific antibody, and (ii) the structures of several major insect allergens, as specified below.(A) Recently, we have determined the first B-cell epitope of Hya from the crystallographic structure determination of Hya in complex with Fab fragment of the monoclonal anti-Hya antibody which is competing with patients IgE for Hya binding. New B-cell epitopes of bee venom hyaluronidase shall be identified by structure determination of Hya in complex(es) with Fab fragments derived from two different anti-Hya monoclonal antibodies. The epitope knowledge provided by the structure may then be used to design hypoallergenic derivatives which can be exploited as potential allergy vaccines since they would exhibit a reduced risk of anaphylaxis but still preserve their immunogenic features.(B) Serine proteases from the venoms of the honey bee (Api m 7) and paper wasp (Pol d 4) are putative major allergens since they arerecognised by IgE antibodies from the sera of a majority of the bee venom allergic patients. The structure determination of this new class of Hymenoptera venom allergens is the first and necessary step towards the identification of relevant B-cell epitopes by structural studies of allergen/antibody complexes. It is anticipated that the structural knowledge would help to understand the different properties of these two enzymes with respect to their primary structure and enzymatic activity. The effect of glycosylation on structural, enzymatic and allergenic properties of these enzymes will be investigated by biochemical, biophysical and immunochemical studies.(C) Sol i 3 and Sol i 4 are potent fire ant allergens and are recognized by specific IgE antibodies from the sera of a majority of patients allergic to the fire ant venom. Their function is, as yet, unknown and there is no sequence homologous to Sol i 4. Structure determination will reveal the surface topology and electrostatic potential of these allergens which could be then exploited towards identifying B-cell epitopes.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Crystal structure of Sol I 2: a major allergen from fire ant venom.
Borer Aline S., Wassmann Paul, Schmidt Margit, Hoffman Donald R., Zhou Jing-Jiang, Wright Christine, Schirmer Tilman, Markovic-Housley Zora (2012), Crystal structure of Sol I 2: a major allergen from fire ant venom., in J Mol Biol, 415(4), 635-648.
Recombinant allergen-based IgE testing to distinguish bee and wasp allergy.
Mittermann Irene, Zidarn Mihaela, Silar Mira, Markovic-Housley Zora, Aberer Werner, Korosec Peter, Kosnik Mitja, Valenta Rudolf (2010), Recombinant allergen-based IgE testing to distinguish bee and wasp allergy., in J Allergy Clin Immunol, 125(6), 1300-1307.
High-affinity IgE recognition of a conformational epitope of the major respiratory allergen Phl p 2 as revealed by X-ray crystallography.
Padavattan Sivaraman, Flicker Sabine, Schirmer Tilman, Madritsch Christoph, Randow Stefanie, Reese Gerald, Vieths Stefan, Lupinek Christian, Ebner Christof, Valenta Rudolf, Markovic-Housley Zora (2009), High-affinity IgE recognition of a conformational epitope of the major respiratory allergen Phl p 2 as revealed by X-ray crystallography., in J. Immunol., 182(4), 2141-2151.
Structure of the major carrot allergen {Dau c 1}.
Markovic-Housley Zora, Basle Arnaud, Padavattan Sivaraman, Maderegger Bernhard, Schirmer Tilman, Hoffmann-Sommergruber Karin (2009), Structure of the major carrot allergen {Dau c 1}., in Acta Crystallogr. D Biol. Crystallogr., 65(Pt 11), 1206-1212.
Crystal structure of the major allergen from fire ant venom, Sol i 3.
Padavattan Sivaraman, Schmidt Margit, Hoffman Donald R, Markovic-Housley Zora (2007), Crystal structure of the major allergen from fire ant venom, Sol i 3., in J. Mol. Biol., 383(1), 178-185.
Identification of a B-cell epitope of hyaluronidase, a major bee venom allergen, from its crystal structure in complex with a specific Fab.
Padavattan Sivaraman, Schirmer Tilman, Schmidt Margit, Akdis Cezmi, Valenta Rudolf, Mittermann Irene, Soldatova Lyudmila, Slater Jay, Mueller Ulrich, Markovic-Housley Zora (2007), Identification of a B-cell epitope of hyaluronidase, a major bee venom allergen, from its crystal structure in complex with a specific Fab., in J. Mol. Biol., 368(3), 742-752.
Characterization of the N-glycans of recombinant bee venom hyaluronidase (Api m 2) expressed in insect cells.
Soldatova Lyudmila N., Tsai Chaoming, Dobrovolskaia Ekaterina, Markovic-Housley Zora, Slater Jay E. (2007), Characterization of the N-glycans of recombinant bee venom hyaluronidase (Api m 2) expressed in insect cells., in Allergy Asthma Proc, 28(2), 210-215.

Collaboration

Group / person Country
Types of collaboration
Dr. D Hoffman, USA United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Dr. Tilman Schirmer Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Dr. Rudolf Valenta Austria (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Dr. Margit Schmid United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Dr. U. R. Mueller Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Dr. J-J. Zhou Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Invited lecture, University of Belgrade and Serbian Chemical Society 01.06.2012 Belgrade, Serbia
BIT's 4th Annual International Congress of Antibodies (ICA-2012) 26.03.2012 Beijing, China
XXI World Allergy Congress 2009 06.12.2009 Buenos Aires, Argentina
Invited lecture, Scientific seminar at medical University of Vienna 07.03.2008 Vienna, Medical University


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
Meet&Match Antibody Technologies, organised by Biovalley 31.03.2001 Basel, Switzerland


Communication with the public

Communication Title Media Place Year
Media relations: print media, online media Bessere Therapie fuer Grasspollen-Allergiker Horizonte der Schweizerischen Nationalfonds, Nr.81 German-speaking Switzerland 04.06.2009

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