Published Online: July 2015
X-ray crystallography defines the spatial location of atoms and, therefore, the overall three-dimensional structure or folding of protein molecules. This discipline is now 100 years old. Crystallographic studies have led to the structure determination of allergens, antibodies, receptors, and other molecules involved in immunological processes and allergic disease.
The article by Pomés et al. recently published in The Journal of Allergy and Clinical Immunology (JACI), is a tribute to the contributions of X-ray crystallography to Allergy and Clinical Immunology. The first enzyme structure to be determined was lysozyme in 1965, also known as egg allergen Gal d 4. Nowadays, the Protein Data Bank (PDB) (www.rcsb.org) contains the three-dimensional structures of over 100 allergens, representing approximately 50 protein families, whose structures are as diverse as their biological functions. Structures of molecular complexes involved in immunological processes include peptides presented by MHC class II molecules, cytokines bound to their receptors, allergen-antibody complexes, and innate immune receptors with their ligands.
Information derived from crystallographic studies provides critical insights into the function of allergen molecules. Proteolytic activity and ligand binding are strongly associated with allergenicity. Specific amino acids which form catalytic sites or ligand binding sites have been revealed from the three-dimensional structures of dust mite allergens Der p 1 and Der p 2, respectively. Allergen function can also be considered as one of the determinants of environmental exposure, which is essential for IgE sensitization. Structural data defines the molecular surface that is accessible to antibodies and, therefore, determines antibody specificity and the molecular basis for allergen cross-reactivity.
In clinical practice, these are important factors for the selection of allergen panels used for molecular diagnosis and the interpretation of patients’ symptoms. Structural data are the basis for designing modified allergens with reduced IgE reactivity, while preserving T cell epitopes, for immunotherapy. Recombinant allergens have already shown promising results in immunotherapy clinical trials. This review celebrates the contributions of X-ray crystallography to clinical immunology and allergy, focusing on new molecular perspectives that will complement and improve diagnosis and current treatment of allergic diseases.
The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.