Structure, immunogenicity, and IgE cross-reactivity among cashew, pistachio, and peanut vicilin-buried peptides

Authors: FOO, ALEXANDER - National Institute Of Environmental Health Sciences (NIEHS, NIH); Nesbit, Jacqueline; GIPSON, STEPHEN - Oak Ridge Institute For Science And Education (ORISE); Cheng, Hsiaopo; Hurlburt, Barry; KULIS, MICHAEL - University Of North Carolina; KIM, EDWIN - University Of North Carolina; DRESKIN, STEPHEN - University Of Colorado; Maleki, Soheila; MUELLER, GEOFFREY - National Institute Of Environmental Health Sciences (NIEHS, NIH)

Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/23/2023
Publication Date: 2/9/2022
Citation: Foo, A., Nesbit, J.B., Gipson, S., Cheng, H., Hurlburt, B.K., Kulis, M.D., Kim, E.H., Dreskin, S., Maleki, S.J., Mueller, G. 2022. Structure, immunogenicity, and IgE cross-reactivity among cashew, pistachio, and peanut vicilin-buried peptides. Journal of Agricultural and Food Chemistry. https://doi.org/10.1021/acs.jafc.1c07225.
DOI: https://doi.org/10.1021/acs.jafc.1c07225

Interpretive Summary: Vicillins are a class of proteins often found to be peanut and tree-nut allergens. Whereas the final the large vicillin protein end product contains several IgE antibody reactive sites, the smaller peptides resulting from processing within the nut seed also have IgE antibody binding sites or epitopes. In this study, the vicillin precursor VBPs (Vicillin Buried Peptides) from cashew, pistachio, walnut and peanut were characterized for IgE binding and structure. It was found that all four VBPs had similar 3-dimensional folds and bound IgE. Based on these results it is likely that the IgE epitopes which occupy the same structural regions are a likely cause of IgE cross reactivity between peanuts and tree nuts.

Technical Abstract: Peanut and tree nut allergies are frequently comorbid for reasons not completely understood. Vicilin-buried peptides (VBPs) are derived from the N-terminal leader-sequence (LS) of seed storage proteins and are receiving increasing attention as novel food allergens. Characterizing the VBPs from peanuts and tree nuts may help understand comorbidity and cross-reactivity despite a distant evolutionary origin. Peptide microarrays were used to identify IgE-reactive sequences from the LS of the vicilin allergens from Ara h 1, Ana o 1, Jug r 2, and Pis v 3 using serum from patients diagnosed as peanut monoallergic (PN), peanut and cashew/pistachio co-allergic (PN&CP) or cashew/pistachio monoallergic (CP) patients. The structure of four VBPs were solved using solution-NMR (cashew: AO1.1, AO1.2 and pistachio: PV3.1, PV3.2), and their biophysical properties assessed using in vitro proteolysis assays and circular dichroism. Peptides were identified which bound IgE from PN, PN&CP, and CP patients in the peanut, cashew, walnut, and pistachio LS. IgE binding was frequently observed in the VBP domains AH1.1, AO1.1, JR2.1, and PV3.1, and not in AO1.2, JR2.2, JR2.3, PV3.2 nor the unstructured regions. Comparisons of structural features suggest the VBP scaffold can support cross-reactivity despite low sequence identity. The cashew VBPs are more resistant to proteolysis than the pistachio VBPs, correlating with a slight increase in prevalence. Pistachio and cashew VBPs AO1.1 and PV3.1 are important allergens which support IgE-reactive sequences in PN, PN&CP, and CP patients. The conserved VBP fold could allow for cross-reactivity with peanuts and other tree-nuts including walnut. Differences in the biophysical properties hint that cashew is a more potent sensitizing agent than pistachio.