IgE-Binding Epitopes of Pis v 1, Pis v 2 and Pis v 3, the Pistachio (Pistacia vera) Seed Allergens

Abstract

Sequential IgE-binding epitopes were identified on the molecular surface of the Pis v 1 (2S albumin), Pis v 2 (11S globulin/legumin) and Pis v 3 (7S globulin/vicilin)—major allergens from pistachio (Pistacia vera) seeds—using the Spot technique. They essentially consist of hydrophilic and electropositively charged residues well exposed on the surface of the allergens. Most of the epitopic regions identified on Pis v 1 and Pis v 3 do not coincide with the putative N-glycosylation sites and thus are not considered as glycotopes. Surface analysis of these epitopic regions indicates a high degree of conformational similarity with the previously identified epitopic regions of the corresponding allergens Ana o 1 (vicilin), Ana o 2 (legumin) and Ana o 3 (2S albumin) from the cashew (Anacardium occidentale) nut. These results offer a molecular basis for the IgE-binding cross-reactivity often observed between pistachio and cashew nut. They support the recommendation for prescribing pistachio avoidance in cashew allergic patients. Other conformational similarities were identified with the corresponding allergens Ses i 1 (2S albumin), Ses i 3 (vicilin) and Ses i 6 (legumin) from sesame (Sesamum indicum), and Jug r 1 (2S albumin), Jug r 2 (vicilin) and Jug r 4 (legumin) from walnut (Juglans regia). Conversely, conformation of most of the epitopic regions of the pistachio allergens often differs from that of epitopes occurring on the molecular surface of the corresponding Ara h 1 (vicilin), Ara h 2 (2S albumin) and Ara h 3 (legumin) allergens from peanut (Arachis hypogaea).

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

“…18 Curiously, a PD search comparing the tomato and buckwheat VBPs shown in Figure S2 against this same 13cp reveals comparable scores to the peanut/walnut VBPs, suggesting that this mode of cross-reactivity is applicable to other food allergen sources beyond the peanut and walnut sequences described in this work. Finally, it should also be noted that IgE-reactive VBPs have also been identified in almonds (Pru du 8), 46 cashew (Ana o 1), 47 pistachio (Pis v 3), 48,49 sesame (Ses i 3), 49 and macadamia nut (Mac i 1). 50 While the structure of these IgE-reactive VBPs has yet to be solved, their sequences share similar PD scores when compared against the 13cp as their peanut and walnut homologues.…”

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

“…50 Nonetheless, it is becoming increasingly evident that plant VBPs represent an important immunogenic species that can mediate both allergic sensitization and cross-reactive IgE binding across a range of common food sources including peanuts and tree-nuts. Recent works identifying IgE-reactive sequences on VBPs from macadamia nuts, sesame, and almonds 7,10,15,51 further emphasize their immunological potential. The structural and immunological data presented in this work suggests that VBPs from cashews and pistachios could mediate both cashew/pistachio allergy and cross-reactivity with peanut and other tree-nut counterparts via a conserved hairpin motif, with implications for both molecular diagnostic and allergen avoidance strategies.…”

“…The vicilin protein is expressed with an N-terminal leader sequence (LS), which contains a variable number of vicilin-buried peptides (VBPs) that are cleaved from the parent vicilin during the maturation process . IgE-reactive VBPs have been identified in peanuts and tree-nuts such as walnuts, cashews, and pistachios. − The allergen vicilin with the most VBPs is the recently described hazelnut allergen Cor a 16 with a dozen . Previous studies on the peanut LS that contains one VBP domain (AH1.1) revealed that IgE binding levels are uncorrelated to its larger parent vicilin, suggesting that these VBP sequences represent a new allergen family whose immunological properties are independent of their parent vicilins …”

“…In addition to peanuts and walnuts, IgE-reactive VBPs have been identified in various other nut species including almonds, cashew, and pistachio. ,, The latter two are an interesting study: cashews and pistachios generally have different cross-reactivity patterns of IgE binding compared to walnuts and other tree-nuts. , However, the shared VBP motif could potentially mediate cross-reactivity across these patient pools regardless of initial sensitizing agent. Thus, characterizing the IgE reactivity of the cashew and pistachio VBPs would uncover the role of VBP allergens in cross-reactivity, and the structural/biophysical basis for such an interaction.…”

Nut Allergenicity: Effect of Food Processing

“…Most of the epitopic regions of Pis v 1 and Pis v 3 showed a high degree of similarity with the Ana o 1, Ana o 2 and Ana o 3 epitopes. This is considered to be the molecular basis for the IgE-binding cross-reactivity observed between pistachios and cashews [29]. In almonds, six allergenic proteins have been characterized: Pru du 3 (LTP), Pru du 4 (profilin), Pru du 5 (60S ribosomal protein), Pru du 6 (11S legumin), Pru du 8 (antimicrobial seed storage protein) and Pru du 10 (mandelonitrile lyase 2) [30].…”