Molecular basis of allergic cross-reactivity between group 1 major allergens from birch and apple

Patients allergic to birch pollen often also react with fruits and vegetabl es, such as apple. The major cause of cross-reactivity between birch and ap ple is biochemical and immunological similarity between the major allergens , Bet v 1 and Mal d 1, as demonstrated by serological and cellular immunoas says. In addition, birch pollen-specific therapeutic allergy vaccination ha s been shown to improve allergic symptoms caused by oral ingestion of apple . Detailed analysis of molecular surface areas based on the crystal structu re of Bet v 1,,and primary sequence alignment, identify potential epitopes for cross-reactive antibodies. Two or more conserved patches are identified when comparing Bet v 1 and Mal d 1, thus providing a molecular model for s erological cross-reactivity involving more than one IgE-binding epitope. A minimum of two epitopes would be necessary for cross-linking of receptor bo und IgE in functional histamine release assays and skin test. Individual am ino acid substitutions, as occurring in isoallergenic variation, may, howev er, have a dramatic effect on epitope integrity if critical residues are af fected. Thus, one area large enough to accommodate antibody-binding epitope s shared by all known Mal d 1 isoallergens and variants is identified, as w ell as areas shared by Bet v 1 and individual Mal d 1 isoallergens or varia nts. The occurrence of limited epitope coincidence between Bet v 1 and Mal d 1 is in agreement with the observation that some, but not all, birch poll en allergic patients react with apple, and that the epitope repertoire reco gnised by the IgE of the individual patients determines the degree of cross -reactivity. (C) 2001 Elsevier Science B.V. All rights reserved.