Amb a 1 isoforms: Unequal siblings with distinct immunological features

Abstract

BackgroundRagweed 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.MethodsAfter 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.ResultsAmb 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.ConclusionThe 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.

Epitope Mapping of Major Ragweed Allergen Amb a 1

“…In previous study, Amb a 1.01 showed higher IgE-binding activity compared to Amb a 1.02 or 03 isoforms. 12 Therefore, we used Amb a 1.01 isoform for in silico linear alignment and conformational epitope mapping. The sequences of 17 different peptides were arranged into six groups according to their degree of similarity (Fig.…”

“…11 They display distinct patterns of IgE binding and immunogenicity with limited B-and T-cell cross-reactivity patterns. 12 Amb a 1 is cross-reactive with its homologous allergen in mugwort pollen Art v 6, a pectate lyase with 65% of sequence identity with Amb a 1. [13][14][15] The identification of relevant epitopes can reveal the molecular basis of allergenic cross-reactivity.…”

Ragweed Pollen Allergy: Burden, Characteristics, and Management of an Imported Allergen Source in Europe

“…material). Immunological characterization of these 5 isoforms revealed different IgE-binding capacities, indicating that Amb a 1.01 has the highest allergenic activity [42]. …”

“…However, this recombinant allergen showed a very low IgE binding activity, maybe due to misfolding [41, 50]. Recently, Amb a 1.0301 has been expressed in Pichia pastoris with an IgE reactivity comparable with the native form [42]. …”

Blueprint for the House Dust Mite

“…The dominant allergens of the grass [7,8], ragweed [9], and birch [10] pollens belong to gene families that might be an important determinant for their prevalent and high immune reactivity. The production of proteins from several related genes would not only allow more protein to be produced, and perhaps in different circumstances, but also facilitate binding to a wide range of the antigen-presenting major histocompatibility molecules.…”