Amb a 1 isoforms: unequal siblings with distinct immunological features

Abstract

Background

Ragweed pollen represents a major allergy risk factor. Ragweed extracts contain five different isoforms of the major allergen Amb a 1. However, the immunologic 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 immunologic 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 of 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.

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