The Journal of Allergy and Clinical Immunology
Volume 119, Issue 4 , Pages 944-951 , April 2007

Allergenicity and antigenicity of wild-type and mutant, monomeric, and dimeric carrot major allergen Dau c 1: Destruction of conformation, not oligomerization, is the roadmap to save allergen vaccines

  • Gerald Reese, PhD

      Affiliations

    • From the Paul Ehrlich Institut, Department of Allergology, Langen
    • Corresponding Author InformationReprint requests: Gerald Reese, PhD, Paul-Ehrlich-Institut, Department of Allergology, Paul-Ehrlich-Str 51-59, D-63325 Langen, Germany.
    • ,
  • Barbara K. Ballmer-Weber, MD

      Affiliations

    • University Hospital, Allergy Unit, Department of Dermatology, Zurich
    • ,
  • Andrea Wangorsch, MS

      Affiliations

    • From the Paul Ehrlich Institut, Department of Allergology, Langen
    • ,
  • Stefanie Randow

      Affiliations

    • From the Paul Ehrlich Institut, Department of Allergology, Langen
    • ,
  • Stefan Vieths, PhD

      Affiliations

    • From the Paul Ehrlich Institut, Department of Allergology, Langen

Received 4 October 2006 ,Revised 28 November 2006 ,Accepted 30 November 2006.

References 

  1. Lin X, Hwang GJ, Zimmerman JL. Isolation and characterization of a diverse set of genes from carrot somatic embryos. Plant Physiol. 1996;112:1365–1374
  2. Ballmer-Weber BK, Wangorsch A, Bohle B, Kaul S, Kundig T, Fotisch K, et al. Component-resolved in vitro diagnosis in carrot allergy: does the use of recombinant carrot allergens improve the reliability of the diagnostic procedure?. Clin Exp Allergy. 2005;35:970–978
  3. Yamamoto M, Torikai S, Oeda K. A major root protein of carrots with high homology to intracellular pathogenesis-related (PR) proteins and pollen allergens. Plant Cell Physiol. 1997;38:1080–1086
  4. Hoffmann-Sommergruber K, O'Riordain G, Ahorn H, Ebner C, Laimer Da Camara Machado M, Puhringer H, et al. Molecular characterization of Dau c 1, the Bet v 1 homologous protein from carrot and its cross-reactivity with Bet v 1 and Api g 1. Clin Exp Allergy. 1999;29:840–847
  5. Vieths S, Scheurer S, Ballmer-Weber B. Current understanding of cross-reactivity of food allergens and pollen. Ann N Y Acad Sci. 2002;964:47–68
  6. Ballmer-Weber BK, Wuthrich B, Wangorsch A, Fotisch K, Altmann F, Vieths S. Carrot allergy: double-blinded, placebo-controlled food challenge and identification of allergens. J Allergy Clin Immunol. 2001;108:301–307
  7. Helbling A, Lopez M, Schwartz HJ, Lehrer SB. Reactivity of carrot-specific IgE antibodies with celery, apiaceous spices, and birch pollen. Ann Allergy. 1993;70:495–499
  8. Bohle B, Radakovics A, Luttkopf D, Jahn-Schmid B, Vieths S, Ebner C. Characterization of the T cell response to the major hazelnut allergen, Cor a 1.04: evidence for a relevant T cell epitope not cross-reactive with homologous pollen allergens. Clin Exp Allergy. 2005;35:1392–1399
  9. Hansen KS, Khinchi MS, Skov PS, Bindslev-Jensen C, Poulsen LK, Malling HJ. Food allergy to apple and specific immunotherapy with birch pollen. Mol Nutr Food Res. 2004;48:441–448
  10. Bolhaar ST, Tiemessen MM, Zuidmeer L, van Leeuwen A, Hoffman-Sommergruber K, Bruijnzeel-Koomen CA, et al. Efficacy of birch-pollen immunotherapy on cross-reactive food allergy confirmed by skin tests and double-blind food challenges. Clin Exp Allergy. 2004;34:761–769
  11. Bucher X, Pichler WJ, Dahinden CA, Helbling A. Effect of tree pollen specific, subcutaneous immunotherapy on the oral allergy syndrome to apple and hazelnut. Allergy. 2004;59:1272–1276
  12. Son DY, Scheurer S, Hoffmann A, Haustein D, Vieths S. Pollen-related food allergy: cloning and immunological analysis of isoforms and mutants of Mal d 1, the major apple allergen, and Bet v 1, the major birch pollen allergen. Eur J Nutr. 1999;38:201–215
  13. Scheurer S, Son DY, Boehm M, Karamloo F, Franke S, Hoffman A, et al. Cross-reactivity and epitope analysis of Pru a 1, the major cherry allergen. Mol Immunol. 1999;36:155–167
  14. Neudecker P, Lehmann K, Nerkamp J, Haase T, Wangorsch A, Fotisch K, et al. Mutational epitope analysis of Pru av 1 and Api g 1, the major allergens of cherry (Prunus avium) and celery (Apium graveolens): correlating IgE reactivity with three-dimensional structure. Biochem J. 2003;376:97–107
  15. Ferreira F, Ebner C, Kramer B, Casari G, Briza P, Kungl AJ, et al. Modulation of IgE reactivity of allergens by site-directed mutagenesis: potential use of hypoallergenic variants for immunotherapy. FASEB J. 1998;12:231–242
  16. Ma Y, Gadermaier G, Bohle B, Bolhaar S, Knulst A, Markovic-Housley Z, et al. Mutational analysis of amino acid positions crucial for IgE-binding epitopes of the major apple (Malus domestica) allergen, Mal d 1. Int Arch Allergy Immunol. 2006;139:53–62
  17. Vrtala S, Hirtenlehner K, Susani M, Akdis M, Kussebi F, Akdis CA, et al. Genetic engineering of a hypoallergenic trimer of the major birch pollen allergen Bet v 1. FASEB J. 2001;15:2045–2047
  18. Gafvelin G, Thunberg S, Kronqvist M, Gronlund H, Gronneberg R, Troye-Blomberg M, et al. Cytokine and antibody responses in birch-pollen-allergic patients treated with genetically modified derivatives of the major birch pollen allergen Bet v 1. Int Arch Allergy Immunol. 2005;138:59–66
  19. Mahler V, Vrtala S, Kuss O, Diepgen TL, Suck R, Cromwell O, et al. Vaccines for birch pollen allergy based on genetically engineered hypoallergenic derivatives of the major birch pollen allergen, Bet v 1. Clin Exp Allergy. 2004;34:115–122
  20. Niederberger V, Valenta R. Molecular approaches for new vaccines against allergy. Expert Rev Vaccines. 2006;5:103–110
  21. Reisinger J, Horak F, Pauli G, van Hage M, Cromwell O, Konig F, et al. Allergen-specific nasal IgG antibodies induced by vaccination with genetically modified allergens are associated with reduced nasal allergen sensitivity. J Allergy Clin Immunol. 2005;116:347–354
  22. Ceska M, Lundkvist U. A new and simple radioimmunoassay method for the determination of IgE. Immunochemistry. 1972;9:1021–1030
  23. Kwok SC, Hodges RS. Clustering of large hydrophobes in the hydrophobic core of two-stranded alpha-helical coiled-coils controls protein folding and stability. J Biol Chem. 2003;278:35248–35254
  24. Holm J, Gajhede M, Ferreras M, Henriksen A, Ipsen H, Larsen JN, et al. Allergy vaccine engineering: epitope modulation of recombinant Bet v 1 reduces IgE binding but retains protein folding pattern for induction of protective blocking-antibody responses. J Immunol. 2004;173:5258–5267
  25. Wiche R, Gubesch M, Konig H, Fotisch K, Hoffmann A, Wangorsch A, et al. Molecular basis of pollen-related food allergy: identification of a second cross-reactive IgE epitope on Pru av 1, the major cherry (Prunus avium) allergen. Biochem J. 2005;385:319–327
  26. Mittag D, Batori V, Neudecker P, Wiche R, Friis EP, Ballmer-Weber BK, et al. A novel approach for investigation of specific and cross-reactive IgE epitopes on Bet v 1 and homologous food allergens in individual patients. Mol Immunol. 2006;43:268–278

 Dr Barbara K. Ballmer-Weber was a recipient of a grant for the promotion of academic young people of the University of Zürich (Stiefel-Zangger-Stiftung) and of the Swiss National Foundation (32-66308.01).Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.

PII: S0091-6749(06)03802-4

doi: 10.1016/j.jaci.2006.11.699

The Journal of Allergy and Clinical Immunology
Volume 119, Issue 4 , Pages 944-951 , April 2007

Article Tools

* Image Usage & Resolution