Molecular modelling of the major peanut allergen Ara h 1 and other homotrimeric allergens of the cupin superfamily: a structural basis for their IgE-binding cross-reactivity.

Three-dimensional models of the major vicilin allergens from peanut (Ara h 1), lentil (Len c 1) and pea (Pis s 1), were built by homology-based modelling from the X-ray coordinates of the structurally closely related soybean beta-conglycinin. All the allergen monomers exhibit the typical cupin motif made of two modules related by a pseudo-dyad axis. Each module consists of a beta-barrel core domain associated to a loop domain which mainly contains alpha-helices. The three cupin motifs are assumed to be arranged in a homotrimeric structure similar to that observed in beta-conglycinin, phaseolin or canavalin. Most of the sequential B-cell epitopes characterized on the C-terminus of the Ara h 1 allergen are well conserved in both Len c 1 and Pis s 1 allergens. They occupy very comparable areas on the molecular surface of the allergens and exhibit a similar three-dimensional conformation. This antigenic community readily accounts for the IgE-binding cross-reactivity commonly observed between the vicilin allergens from edible legume seeds. The clinical implication of this cross-reactivity is addressed for a definite diagnosis of legume seed allergy.