Food, drug, insect sting allergy, and anaphylaxisProtein unfolding strongly modulates the allergenicity and immunogenicity of Pru p 3, the major peach allergen
Section snippets
Allergen preparation
Native Pru p 3 (nPru p 3) was purified from a freshly prepared peach peel extract, as previously described.30, 31 Purified nPru p 3 was reduced and alkylated (R/A) and subsequently dialyzed against PBS buffer to disrupt the tertiary structure of Pru p 3.32 A protocol for the reduction and alkylation is described in the Methods section of this article’s Online Repository at www.jacionline.org.
The protocols for circular dichroism spectroscopy and protease digestion are also described in the
Unfolded Pru p 3 reduces resistance to gastrointestinal digestion
A Pru p 3 folding variant was generated by means of disruption of disulfide bonds on reduction and alkylation. R/A Pru p 3 showed a reduced apparent molecular mass of 6 kDa in contrast to nPru p 3 (9 kDa) on SDS-PAGE (Fig 1, A). Both samples were investigated for structural integrity and stability against gastrointestinal digestion. The circular dichroism spectrum of R/A Pru p 3 revealed a typically unfolded protein in contrast to nPru p 3, showing 2 minima at 208 nm and 222 nm and indicating
Discussion
nsLTPs are important allergens not only in Rosaceae fruits but also in other plant foods, such as vegetables, cereals, and nuts, as well as in different kinds of pollen.23, 24, 36 The protein structure of lipid transfer proteins, an all α-type compact structure with 4 α-helices, is stabilized by 4 intramolecular disulfide bonds. Lipid transfer proteins retain most of their immunogenic and allergenic capacity after passing through the gastrointestinal tract and are capable of eliciting severe
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Boiling down the cysteine-stabilized LTP fold - loss of structural and immunological integrity of allergenic Art v 3 and Pru p 3 as a consequence of irreversible lanthionine formation
2019, Molecular ImmunologyCitation Excerpt :Elucidation of lanthionine establishment upon heat treatment of LTPs represents a first step to better understand structural changes in cysteine-bond stabilized molecules. So far, generation of hypoallergens for allergen specific immunotherapy proved to be extremely challenging when targeting disulfide bond stabilized molecules (Jongejan et al., 2016; Toda et al., 2011; Eichhorn et al., 2019). New insights provided in this study might help to better understand and thus rationally design such hypoallergenic variants of relevant allergens from e.g. peach, peanut and pellitory pollen.
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Supported in part by Paul-Ehrlich-Institut and the Austrian Science Fund, projects SFBF1807-B13 and W1212.
Disclosure of potential conflict of interest: B. Bohle receives research support from the Austrian Science Fund and the Christian Doppler Research Society. S. Vieths is an associate for the Institute for Product Quality; received an honorarium as an expert reviewer from the Food Allergy Resource and Research Program; receives honorarium for an expert seminar from Fresenius Academy; receives research support from the European Union, the German Research Foundation, the Research Fund of the German Food Industry, Monsanto Company, Pioneer Hi-Bred International, the Food Allergy Research and Resource Program, the European Directorate for the Quality of Medicines and Health Care, and the German Ministry for Education and Research; is a member of the executive committee for the European Academy of Allergy and Clinical Immunology; has served as chairman and as secretary of the Allergen Standardization Subcommittee for the International Union of Immunological Societies; is a registered expert for the European Agency for the Evaluation of Medicinal Products and the European Pharmacopoeia Commission; is chairman of Technical Committee 275 Working Group 12 Food Allergens for CEN; and is a member of the Food Allergy Working Group for the German Society for Allergy and Clinical Immunology. The rest of the authors have declared that they have no conflict of interest.
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These authors contributed equally to this work.