Reshaping the Bet v 1 fold modulates T(H) polarization

J Allergy Clin Immunol. 2011 Jun;127(6):1571-8.e9. doi: 10.1016/j.jaci.2011.01.064. Epub 2011 Mar 21.


Background: Several alternative mechanisms have been proposed to explain why some proteins are able to induce a T(H)2-biased and IgE-mediated immune response. These include specific interactions with receptors of the innate immune system, proteolytic activities, allergen-associated carbohydrate structures, and intrinsic structural determinants.

Objectives: Available data suggest that a fold-dependent allergy-promoting mechanism could be a driving force for the T(H)2-polarization activity of Bet v 1, the major birch pollen allergen.

Methods: Computer-aided sequence and fold analysis of the Bet v 1 family identified a short stretch susceptible for mutations inducing an altered fold of the entire molecule. With this knowledge, 7 consecutive amino acids of Bet v 1 were replaced with the homologous Mal d 1 sequence, creating the derivative BM4.

Results: The minimal changes of the sequence led to a loss of the Bet v 1-like fold and influenced the immunologic behavior. Compared to wild-type Bet v 1, BM4 induced elevated T-cell proliferation of human PBMCs. In the mouse model, immunization with Bet v 1 absorbed to aluminum hydroxide triggered strong T(H)2 polarization, whereas BM4 immunization additionally recruited T(H)1 cells. Furthermore, the fold variant BM4 showed enhanced uptake by dendritic cells and a decreased susceptibility to endo-/lysosomal proteolysis.

Conclusion: Modifications in the 3-dimensional structure of Bet v 1.0101 resulted in a change of its immunologic properties. We observed that the fold alteration led to a modified crosstalk with dendritic cells and a shift of the immune response polarization toward a mixed T(H)1/T(H)2 cytokine production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / chemistry*
  • Allergens / genetics
  • Allergens / immunology*
  • Amino Acid Sequence
  • Animals
  • Antigen-Antibody Reactions
  • Antigens, Plant / chemistry*
  • Antigens, Plant / genetics
  • Antigens, Plant / immunology*
  • Betula / genetics
  • Betula / immunology*
  • Cell Proliferation
  • Dendritic Cells / immunology
  • Epitopes / chemistry
  • Epitopes / genetics
  • Epitopes / immunology
  • Female
  • Humans
  • Immunization
  • In Vitro Techniques
  • Mice
  • Mice, Inbred BALB C
  • Models, Animal
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Protein Folding
  • Rhinitis, Allergic, Seasonal / immunology
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Th1 Cells / immunology
  • Th2 Cells / immunology


  • Allergens
  • Antigens, Plant
  • Epitopes
  • Bet v 1 allergen, Betula