Epitopes with similar physicochemical properties contribute to cross reactivity between peanut and tree nuts

Authors: Nesbit, Jacqueline; SCHEIN, CATHERINE - University Of Texas; BRAUN, BENJAMIN - Stanford University; GIPSON, STEPHEN - Oak Ridge Institute For Science And Education (ORISE); Cheng, Hsiaopo; Hurlburt, Barry; Maleki, Soheila

Submitted to: Molecular Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/26/2020
Publication Date: 5/19/2020
Citation: Nesbit, J.B., Schein, C.H., Braun, B.A., Gipson, S.A., Cheng, H., Hurlburt, B.K., Maleki, S.J. 2020. Epitopes with similar physicochemical properties contribute to cross reactivity between peanut and tree nuts. Molecular Immunology. https://doi.org/10.1016/j.molimm.2020.03.017.
DOI: https://doi.org/10.1016/j.molimm.2020.03.017

Interpretive Summary: Many individuals with peanut (PN) allergy have severe reactions to tree nuts (TN) such as walnuts or cashews. Although allergenic proteins in TN and PN have overall low identity, they share discrete sequences similar in physicochemical properties (PCP) to known IgE epitopes. Here, PCP-consensus peptides (cp, 13 aa and 31 aa) were identified from an alignment of epitope rich regions of walnut vicilin, Jug r 2, leader sequence (J2LS) and cross-reactive epitopes in the 2S albumins of peanut and synthesized. A peptide similarity search in the Structural Database of Allergenic Proteins (SDAP) revealed a network of peptides similar (low property distance, PD) to the 13 aa cp (13cp) in many different plant allergens. Peptides similar to the 13cp in PN and TN allergens bound IgE from sera of patients allergic to PN and TN in peptide microarray analysis. The 13cp was used to produce a rabbit consensus peptide antibody (cpAB) detected proteins that contained repeats similar to the 13cp in western blots of various nut extracts, where reactive proteins were identified by mass spectrometry. The cpAB bound more specifically to allergens and nut extracts containing multiple repeats similar to the 13 cp, such as almond (Pru du 6), peanut (Ara h 2) and walnut (Jug r 2). IgE binding to various nut extracts is inhibited by recombinant J2LS sequence and synthetic 31cp. Thus, several repeated sequences similar to the 13cp are bound by IgE. Multiple similar repeats in several allergens could account for reaction severity and clinically relevant cross-reactivity to PN and TN. These findings may help improve detection, diagnostic, and therapeutic tools.

Technical Abstract: People with allergy to peanut often have allergy to various tree nuts. We hypothesized that a lot of this is due to cross-reactivity of the IgE antibodies that cause the allergic reaction. In this work we used a combination of computational and experimental techniques to identify regions of the proteins that cause the allergic reaction that cause the cross-reactivity between peanut proteins and tree nut proteins.