Molecular Basis of Plant Profilins’ Cross-Reactivity

Abstract

Profilins are ubiquitous allergens with conserved structural elements. Exposure to profilins from different sources leads to IgE-cross-reactivity and the pollen–latex–food syndrome. Monoclonal antibodies (mAbs) that cross-react with plant profilins and block IgE-profilin interactions are relevant for diagnosis, epitope mapping, and specific immunotherapy. We generated IgGs mAbs, 1B4, and 2D10, against latex profilin (anti-rHev b 8) that inhibit the interaction of IgE and IgG4 antibodies from sera of latex- and maize-allergic patients by 90% and 40%, respectively. In this study, we evaluated 1B4 and 2D10 recognition towards different plant profilins, and mAbs recognition of rZea m 12 mutants by ELISAs. Interestingly, 2D10 highly recognized rArt v 4.0101 and rAmb a 8.0101, and to a lesser extent rBet v 2.0101, and rFra e 2.2, while 1B4 showed recognition for rPhl p 12.0101 and rAmb a 8.0101. We demonstrated that residue D130 at the α-helix 3 in profilins, which is part of the Hev b 8 IgE epitope, is essential for the 2D10 recognition. The structural analysis suggests that the profilins containing E130 (rPhl p 12.0101, rFra e 2.2, and rZea m 12.0105) show less binding with 2D10. The distribution of negative charges on the profilins’ surfaces at the α-helices 1 and 3 is relevant for the 2D10 recognition, and that may be relevant to explain profilins’ IgE cross-reactivity.

An Overview of Fruit Allergens: Structural, Functional, Phylogenetical, and Clinical Aspects

“…Recently, the distribution of negative charges on the molecular surface of various profilins, including Amb a 4 and Amb a 8 from Ambrosia artemisiifolia, Art v 4 from Artemisia vulgaris, Bet v 2 from Betula verrucosa, Fra e 2 from Fraxinus excelsior, Hev b 8 from Hevea brasiliensis, Phl p 2 from Phleum pratense, and Zea m 12 from Zea mays, was relevant for the recognition of profilins by monoclonal antibodies, and should participate in their IgE-binding cross-reactivity [42].…”