Allergen protein families and cross-reactivity

Abstract

Allergies are defined as an excessive reaction of the immune system to normally harmless proteins. What makes a protein an allergen, and why are some individuals affected but not others? This review deals with several issues which may provide answers to these crucial questions. From combined researches in allergen and protein databases, it appears that allergens represent only a narrow distribution regarding protein family membership and biological function. By far most allergies are caused by six plant food and pollen protein families, and by four food and airway-exposed protein families from animal sources. The majority of these allergens are cross-reactive: They are not capable of sensitization by themselves, but provoke allergic reactions via IgE binding in sensitized individuals. Analysis of 3D models of allergens representing the most important allergen protein families revealed that, in particular, highly exposed lysine residues on the surface of allergens were involved in IgE binding. Other amino acids that were frequently found in epitopes were alanine, serine, aparagine and glycine. In the birch pollen allergen Bet v 1, these amino acids accounted for 40% of the total amino acid content, with lysine on top (10%). The existence of a limited number of specific motifs in epitopes formed by these amino acids with a major role for alanine is suggested as a general cause of allergies in genetically predisposed individuals. Knowledge on true-sensitizing allergens is still largely lacking. The extended genomic and proteomic knowledge on the Bet v 1 in birch and its cross-reactive homolog Mal d 1 in apple may form a good basis to further elucidate the fundamental questions on allergic sensitization and cross-reactivity.