Amb a 1 isoforms: Unequal siblings with distinct immunological features

Allergy. 2017 Dec;72(12):1874-1882. doi: 10.1111/all.13196. Epub 2017 Jun 14.


Background: Ragweed pollen represents a major allergy risk factor. Ragweed extracts contain five different isoforms of the major allergen Amb a 1. However, the immunological characteristics of Amb a 1 isoforms are not fully investigated. Here, we compared the physicochemical and immunological properties of three most important Amb a 1 isoforms.

Methods: After purification, the isoforms were physicochemically characterized, tested for antibody binding and induction of human T-cell proliferative responses. Their immunological properties were further evaluated in vitro and in vivo in a mouse model.

Results: Amb a 1 isoforms exhibited distinct patterns of IgE binding and immunogenicity. Compared to Amb a 1.02 or 03 isoforms, Amb a 1.01 showed higher IgE-binding activity. Isoforms 01 and 03 were the most potent stimulators of patients' T cells. In a mouse model of immunization, Amb a 1.01 induced higher levels of IgG and IgE antibodies when compared to isoforms 02 and 03. Interestingly, ragweed-sensitized patients also displayed an IgG response to Amb a 1 isoforms. However, unlike therapy-induced antibodies, sensitization-induced IgG did not show IgE-blocking activity.

Conclusion: The present study showed that naturally occurring isoforms of Amb a 1 possess different immunogenic and sensitizing properties. These findings should be considered when selecting sequences for molecule-based diagnosis and therapy for ragweed allergy. Due to its high IgE-binding activity, isoform Amb a 1.01 should be included in diagnostic tests. In contrast, due to their limited B- and T-cell cross-reactivity patterns, a combination of different isoforms might be a more attractive strategy for ragweed immunotherapy.

Keywords: Amb a 1 allergen; allergenicity; cross-reactivity; immunogenicity; ragweed pollen allergy.

MeSH terms

  • Allergens / chemistry
  • Allergens / immunology*
  • Ambrosia / chemistry
  • Ambrosia / immunology*
  • Animals
  • Antigens, Plant / chemistry
  • Antigens, Plant / immunology*
  • Cross Reactions / immunology
  • Disease Models, Animal
  • Female
  • Humans
  • Immune Sera / immunology
  • Immunoglobulin E / immunology
  • Immunoglobulin G / immunology
  • Mice
  • Phenotype*
  • Plant Extracts / chemistry
  • Plant Extracts / immunology
  • Plant Proteins / chemistry
  • Plant Proteins / immunology*
  • Protein Isoforms
  • Rhinitis, Allergic, Seasonal / diagnosis*
  • Rhinitis, Allergic, Seasonal / immunology*
  • Siblings*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism


  • Allergens
  • Amb a I protein, Ambrosia artemisiifolia
  • Antigens, Plant
  • Immune Sera
  • Immunoglobulin G
  • Plant Extracts
  • Plant Proteins
  • Protein Isoforms
  • ragweed pollen
  • Immunoglobulin E