A hypoallergenic variant of the major birch pollen allergen shows distinct characteristics in antigen processing and T-cell activation

Allergy. 2012 Nov;67(11):1375-82. doi: 10.1111/all.12016. Epub 2012 Sep 13.


Background: BM4 is a novel genetically engineered variant of the major birch pollen allergen Bet v 1 that lacks the typical Bet v 1-like fold and displays negligible IgE-binding but strong T cell-activating capacity. The aim of this study was to elucidate possible differences between BM4 and Bet v 1 in internalization, antigen processing, and presentation.

Methods: Proliferative responses to BM4 and Bet v 1 of peripheral blood mononuclear cells and Bet v 1-specific T-cell clones were compared. Fluorescently labeled BM4 and Bet v 1 were used to study surface binding, endocytosis, and intracellular degradation by monocyte-derived DC (mdDC). Both proteins were digested by endolysosomal extracts of mdDC. BM4- and Bet v 1-pulsed mdDC were employed to assess the kinetics of activation of Bet v 1-specific T-cell clones and the polarization of naïve T cells.

Results: BM4 displayed a significantly stronger T cell-activating capacity than Bet v 1. Furthermore, BM4 showed increased surface binding and internalization as well as faster endolysosomal degradation compared with Bet v 1. BM4-pulsed mdDC induced enhanced proliferative responses at earlier time-points in Bet v 1-specific T-cell clones and promoted less IL-5 production in T cells than Bet v 1-pulsed mdDC.

Conclusion: The loss of the Bet v 1-fold changes the protein's interaction with the human immune system at the level of antigen-presenting cells resulting in altered T-cell responses. By combining low IgE-binding with strong and modulating T cell-activating capacity, BM4 represents a highly interesting candidate for specific immunotherapy of birch pollen allergy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology*
  • Amino Acid Sequence
  • Antigen Presentation*
  • Antigens, Plant / chemistry
  • Antigens, Plant / immunology*
  • Antigens, Plant / metabolism
  • Betula / immunology*
  • Cell Polarity
  • Humans
  • Lymphocyte Activation*
  • Molecular Sequence Data
  • Pollen / immunology*
  • T-Lymphocytes / immunology*


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