The importance of recombinant allergens for diagnosis and therapy of IgE-mediated allergies

In the past 10 years, a considerable number of cDNAs coding for allergens h ave been isolated and expressed. Intensive investigations showed that recom binant allergens and their respective natural counterparts possess comparab le properties with respect to structure, function and interaction with the immune system. Recent studies documented that in vitro as well as in vivo d iagnosis of IgE-mediated allergic diseases can be successfully improved by the application of recombinant allergens. In addition, new strategies for a safer specific immunotherapy (SIT) have been developed based on the knowle dge of the primary structures of allergens. Naturally occurring isoforms of allergens as well as recombinant allergens with modified amino acid sequen ces show very low IgE binding capacity but strong T cell-stimulatory activi ty and represent possible candidates. In case of Bet v 1,the major birch po llen allergen, isoforms d, g and I and a Bet v la mutant, produced by site- directed mutagenesis resulting in 6 amino acid exchanges, fulfilled the abo ve mentioned criteria. In a third approach, two adjacent peptides covering the entire Bet v la sequence were produced in an Escherichia coli expressio n system. These peptides contained most of the relevant T cell epitopes, bu t lost their IgE binding capacity and, thus, their ability to activate mast cells and basophils of sensitized patients. Our results suggest that aller gen variants (isoforms, mutants, T cell epitope-containing peptides) may be used as 'hypoallergenic agents' in SIT.