Structure and IgE Cross-Reactivity among Cashew, Pistachio, Walnut, and Peanut Vicilin-Buried Peptides

Abstract

Peanut and tree-nut allergies are frequently comorbid for reasons not completely understood. Vicilin-buried peptides (VBPs) are an emerging family of food allergens whose conserved structural fold could mediate peanut/tree-nut co-allergy. Peptide microarrays were used to identify immunoglobulin E (IgE) epitopes from the N-terminus of the vicilin allergens Ara h 1, Ana o 1, Jug r 2, and Pis v 3 using serum from three patient diagnosis groups: monoallergic to either peanuts or cashew/pistachio, or dual allergic. IgE binding peptides were highly prevalent in the VBP domains AH1.1, AO1.1, JR2.1, and PV3.1, but not in AO1.2, JR2.2, JR2.3, and PV3.2 nor the unstructured regions. The IgE profiles did not correlate with diagnosis group. The structure of the VBPs from cashew and pistachio was solved using solution-NMR. Comparisons of structural features suggest that the VBP scaffold from peanuts and tree-nuts can support cross-reactivity. This may help understand comorbidity and cross-reactivity despite a distant evolutionary origin.

Identification, Characterization, Cloning, and Cross-Reactivity of Zan b 2, a Novel Pepper Allergen of 11S Legumin

“…Cashew nuts, pistachios, and peanuts have been studied more internationally, and allergenic protein fractions have been reported considerably. , Peanut and tree nut allergies are often comorbid and prone to cross-reactivity, possibly because of the structural features, the Vicilin-buried peptides (VBP) scaffolding in peanuts and tree nuts . Despite the considerable structural homology and amino acid sequence identity between nuts and peanuts, , and the potential cross-reactivity between nuts and Sichuan peppers, our study showed that serum IgE from Sichuan pepper-allergic patients binds to the 11S legume protein, as well as to the two nuts of cashews and pistachios apparently, but they did not bind to peanut extracts (Figure B,C).…”

Mutation of Disulfide Bond Sites Reduces the Immunoreactivity of Cra a 4 by Changing the Structural Characteristics

“…38 The disulfide bond was a critical factor for maintaining conformational stability, and the preservation of disulfide bonds is crucial for the binding of IgE to allergens. 39 Zhou et al found that all disulfide bonds were destroyed and the allergenicity of the mutant was decreased when the C mutated into G. 40 In the previous study, the disulfide bond of Scy p 4 was destroyed by the DDT treatment, and the IgG-/IgE-binding activity of Scy p 4 was reduced, which indicated that the disulfide bond was important for IgE-binding to SCP. 15 In this study, C 97 A had the lowest immunoreactivity.…”

“…Site-directed mutation can be used to modify critical amino acids of disulfide bond sites, conformational epitopes, or calcium-binding sites into alanine, which is a good means of manipulating allergenic structure at the molecular level . The disulfide bond was a critical factor for maintaining conformational stability, and the preservation of disulfide bonds is crucial for the binding of IgE to allergens . Zhou et al found that all disulfide bonds were destroyed and the allergenicity of the mutant was decreased when the C mutated into G .…”

Food Allergens of Plant Origin

“…The structures of the cC3C of the VLP of Ara h 1, the two individual cC3C repeats of the VLP of Ana o 1 and Pis v 3, and three cC3C repeats of the VLP of Jug r 2 have been determined by NMR [104,105]. The structures of such cC3C are typical disulfide bond stabilized helix hairpins and the best model of the structure bundle of the second cC3C repeat of Jug r 2 is shown in Figure 1E.…”

“…The VLP was also referred to as vicilin buried peptide [104,105]. However, none of the known structures of vicilins included the VLP region of proteins.…”