Preventive Administration of Non-Allergenic Bet v 1 Peptides Reduces Allergic Sensitization to Major Birch Pollen Allergen, Bet v 1

IgE-mediated allergy to birch pollen affects more than 100 million patients world-wide. Bet v 1, a 17 kDa protein is the major allergen in birch pollen responsible for allergic rhinoconjunctivitis and asthma in birch pollen allergic patients. Allergen-specific immunotherapy (AIT) based on therapeutic administration of Bet v 1-containing vaccines is an effective treatment for birch pollen allergy but no allergen-specific forms of prevention are available. We developed a mouse model for IgE sensitization to Bet v 1 based on subcutaneous injection of aluminum-hydroxide adsorbed recombinant Bet v 1 and performed a detailed characterization of the specificities of the IgE, IgG and CD4+ T cell responses in sensitized mice using seven synthetic peptides of 31-42 amino acids length which comprised the Bet v 1 sequence and the epitopes recognized by human CD4+ T cells. We then d.emonstrate that preventive systemic administration of a mix of synthetic non-allergenic Bet v 1 peptides to 3-4 week old mice significantly reduced allergic immune responses, including IgE, IgG, IgE-mediated basophil activation, CD4+ T cell and IL-4 responses to the complete Bet v 1 allergen but not to the unrelated major grass pollen allergen Phl p 5, without inducing Bet v 1-specific allergic sensitization or adaptive immunity. Our results thus demonstrate that early preventive administration of non-allergenic synthetic T cell epitope-containing allergen peptides could be a safe strategy for the prevention of allergen-specific IgE sensitization.

Bet v 1 potential allergens are involved in anthracnose resistance of strawberry varieties

BACKGROUND: Bet v 1 family identified as one major plant food allergen class, is highly homologous to pathogenesis-related protein 10 (PR-10), but its biological function involved in disease resistance is still unclear. OBJECTIVE: This study aims to investigate whether Bet v 1 potential allergens participate in the resistance of berry crops against fungal pathogen. METHODS: Allergenicity of Bet v 1 proteins in strawberry (Fragaria) was evaluated by bioinformatics methods. Their expression in response to anthracnose and between susceptible and resistance varieties was analyzed. RESULTS: 19 Bet v 1 homologous proteins were identified and 15 of them were considered as allergen candidates. RNA-seq analysis indicated most of these Fra a 1s expressed in fruits could be largely induced by the invasion of anthracnose pathogen Colletotrichum. The mRNA level of fruit major allergen Fra a 1.05 in the resistant variety Shenyang (SY) was 20∼50 fold higher compared with those in the susceptible cultivar and two diploid wild species. Immunoblotting using Birch (Betula pendula) Bet v 1 allergen-specific IgG antibody confirmed the large-scale accumulation of potential cross-reactive antigens in SY fruit. CONCLUSIONS: Strawberry Bet v 1 potential allergens exhibit their correspondence with anthracnose resistance that might be instructive to future breeding strategies.

Possibilities of interlinking the genomic data and allergenic potential of apples

Apple allergy belongs to the most prevalent fruit allergies which in North and Central Europe is mainly attributed to cross-reaction between Bet v 1 allergen from birch pollen and Mal d 1 major apple allergen. For a long time, patients observed symptoms of unequal severity after consumption of different apple cultivars. This led scientific community to search for the basis of the cultivar-specific allergenicity. According to several studies, the amount of Mal d 1 allergen plays an important role. Currently, notable attention is mainly concentrated on genetic variability as the primary source of different allergenic potential. Mal d 1 gene family is a large family of gene isoforms and their variants differing in the primary sequence. These sequence alternations may cause changes in protein structure and potentially affect the binding capacity to IgE and thus the allergenic potential. Among many methods available to analyze genetic variability, restriction fragment length polymorphism is simple technique suitable to analyze variability of Mal d 1 allergen. This paper aims to provide a brief overview of a possible approach of interlinking genomic data (e.g. as by RFLP profiles) and clinically proven apple allergenicity.