|FOO, ALEXANDER - National Institute Of Environmental Health Sciences (NIEHS, NIH)|
|GIPSON, STEPHEN - Oak Ridge Institute For Science And Education (ORISE)|
|BUSCHEL, PETER - National Institute Of Environmental Health Sciences (NIEHS, NIH)|
|DEROSE, EUGENE - National Institute Of Environmental Health Sciences (NIEHS, NIH)|
|SCHEIN, CATHERINE - University Of Texas Medical Branch|
|TEUBER, SUZANNE - University Of California, Davis|
|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: 1/20/2022
Publication Date: 2/9/2022
Citation: Foo, A.C.Y., Nesbit, J.B., Gipson, S.A.Y., Cheng, H., Buschel, P., Derose, E.F., Schein, C.H., Teuber, S.S., Hurlburt, B.K., Maleki, S.J., Mueller, G.A. 2022. Structure, immunogenicity, and IgE cross-reactivity among walnut and peanut vicilin buried peptides. Journal of Agricultural and Food Chemistry. 70(7):2389-2400. 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 post-translational processing also have IgE binding sites or epitopes. In this study, the vicillin precursor VBPs (Vicillin Buried Peptides) from peanut and walnut 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 walnuts.
Technical Abstract: Vicilin Buried Peptides (VBPs) from edible plants are derived from the N-terminal leader sequences (LS) of seed storage proteins. VBPs are defined by a common a-hairpin fold mediated by conserved CxxxCx(10-14)CxxxC motifs. Here, peanut and walnut VBPs were characterized as potential mediators of both peanut/walnut allergenicity and cross-reactivity despite their low (~17%) sequence identify. The structures of one peanut (AH1.1) and 3 walnut (JR2.1, JR2.2, JR2.3) VBPs were solved using solution-NMR, revealing similar a-hairpin structures stabilized by disulfide bonds with high levels of surface similarity. Peptide microarrays identified several peptide sequences primarily on AH1.1 and JR2.1 which were recognized by peanut, walnut, and dual-allergic patient IgE, establishing these peanut and walnut VBPs as potential mediators of allergenicity and cross-reactivity. JR2.2 and JR2.3 displayed extreme resilience against endosomal digestion, likely hindering epitope generation and contributing to their reduced allergic potential.