The protein structure determines the sensitizing capacity of Brazil nut 2S albumin (\u3ci\u3eBer e1\u3c/i\u3e) in a rat food allergy model

It is not exactly known why certain food proteins are more likely to sensitize. One of the characteristics of most food allergens is that they are stable to the acidic and proteolytic conditions in the digestive tract. This property is thought to be a risk factor in allergic sensitization. The purpose of the present study was to investigate the contribution of the protein structure of 2S albumin (Ber e1), a major allergen from Brazil nut, on the sensitizing capacity in vivo using an oral Brown Norway rat food allergy model. Disulphide bridges of 2S albumin were reduced and alkylated resulting in loss of protein structure and an increased pepsin digestibility in vitro. Both native 2S albumin and reduced/alkylated 2S albumin were administered by daily gavage dosing (0.1 and 1 mg) to Brown Norway rats for 42 days. Intraperitoneal administration was used as a positive control. Sera were analysed by ELISA and passive cutaneous anaphylaxis. Oral exposure to native or reduced/alkylated 2S albumin resulted in specific IgG1 and IgG2a responses whereas only native 2S albumin induced specific IgE in this model, which was confirmed by passive cutaneous anaphylaxis. This study has shown that the disruption of the protein structure of Brazil nut 2S albumin decreased the sensitizing potential in a Brown Norway rat food allergy model, whereas the immunogenicity of 2S albumin remained preserved. This observation may open possibilities for developing immunotherapy for Brazil nut allergy

Conformational stability of digestion-resistant peptides of peanut conglutins reveals the molecular basis of their allergenicity

Conglutins represent the major peanut allergens and are renowned for their resistance to gastrointestinal digestion. Our aim was to characterize the digestion-resistant peptides (DRPs) of conglutins by biochemical and biophysical methods followed by a molecular dynamics simulation in order to better understand the molecular basis of food protein allergenicity. We have mapped proteolysis sites at the N- and C-termini and at a limited internal segment, while other potential proteolysis sites remained unaffected. Molecular dynamics simulation showed that proteolysis only occurred in the vibrant regions of the proteins. DRPs appeared to be conformationally stable as intact conglutins. Also, the overall secondary structure and IgE-binding potency of DRPs was comparable to that of intact conglutins. The stability of conglutins toward gastro-intestinal digestion, combined with the conformational stability of the resulting DRPs provide conditions for optimal exposure to the intestinal immune system, providing an explanation for the extraordinary allergenicity of peanut conglutins