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 have been isolated and expressed. Intensive investigations showed that recombinant allergens and their respective natural counterparts possess comparable properties with respect to structure, function and interaction with the immune system. Recent studies documented that in vitro as well as in vivo diagnosis 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 knowledge of the primary structures of allergens. Naturally occurring isoforms of allergens as well as recombinant allergens with modified amino acid sequences show very low IgE binding capacity but strong T cell-stimulatory activity and represent possible candidates. In case of Bet v 1, the major birch pollen allergen, isoforms d, g and l and a Bet v 1a mutant, produced by site-directed mutagenesis resulting in 6 amino acid exchanges, fulfilled the above mentioned criteria. In a third approach, two adjacent peptides covering the entire Bet v 1a sequence were produced in an Escherichia coli expression system. These peptides contained most of the relevant T cell epitopes, but lost their IgE binding capacity and, thus, their ability to activate mast cells and basophils of sensitized patients. Our results suggest that allergen variants (isoforms, mutants, T cell epitope-containing peptides) may be used as 'hypoallergenic agents' in SIT.
Kraft
D
D
Institute of General and Experimental Pathology, University of Vienna, Austria.
Ferreira
F
F
Vrtala
S
S
Breiteneder
H
H
Ebner
C
C
Valenta
R
R
Susani
M
M
Breitenbach
M
M
Scheiner
O
O
D000485:Allergens / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D000818:Animals; D052179:Antigens, Plant; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D006967:Hypersensitivity / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology*; D009154:Mutation; D010446:Peptide Fragments / Q000276:immunology; D010940:Plant Proteins / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use
D000485:Allergens; D052179:Antigens, Plant; D018076:DNA, Complementary; D010446:Peptide Fragments; D010940:Plant Proteins; D011994:Recombinant Proteins; C061312:Bet v 1 allergen, Betula; D007073:Immunoglobulin E