Wheat products cause IgE-mediated allergies. The present study aimed to decipher the molecular basis of alpha- and gamma-gliadin allergenicity. Gliadins and their domains, the repetitive N-terminal and the nonrepetitive C-terminal domains, were cloned and expressed in Escherichia coli. Their secondary structures and their IgE binding capacity were compared with those of natural proteins before and after reduction/alkylation. Allergenicity was evaluated with sera from patients who had wheat food allergy or baker's asthma: The secondary structures of natural and recombinant proteins were slightly different. Compared with natural gliadins, recombinant proteins retained IgE binding but with reduced reactivity. Reduction/alkylation decreased IgE binding for both natural and recombinant gliadins. Although more continuous epitopes were identified in the N-terminal domains, of alpha- and gamma-gliadins, both the N-terminal and C-terminal domains contributed to IgE binding. As for other Members of the prolamin: superfamily, disulfide bonds appear to be of high importance for IgE binding.