Can knowledge of the molecular structure of allergens improve immunotherapy?

Conventional immunotherapy may be associated with the development of adverse reactions, including anaphylaxis, due to the use of increasing doses of allergen. Standardization of extracts is necessary in order to assess the correct amount of allergen administered. In recent years, increased knowledge on the molecular structure of allergens has allowed the development of novel alternatives for immunotherapy. Initially, allergens were cloned and expressed as recombinant proteins in eukaryotic and prokaryotic systems. Crystallization of the purified proteins led to the elucidation of the tertiary structure of the allergen. Molecular biology techniques were used to construct modified allergens whose new IgE binding properties were studied. IgE antibody mapping combined with molecular modeling has allowed the recognition of IgE binding sites on the surface of the molecule. This information has been applied to the engineering of new modified allergens, with and without adjuvants, that retain immunogenicity but with reduced allergenicity. The use of these molecules for immunotherapy should allow the administration of greater doses of allergen, without the undesired side effects characteristic of conventional immunotherapy. (C) 2001 Lippincott Williams & Wilkins.