title: 100 Years later: Celebrating the contributions of x-ray crystallography to allergy and clinical immunology.
abstract: Current knowledge of molecules involved in immunology and allergic disease results from the significant contributions of x-ray crystallography, a discipline that just celebrated its 100th anniversary. The histories of allergens and x-ray crystallography are intimately intertwined. The first enzyme structure to be determined was lysozyme, also known as the chicken food allergen Gal d 4. Crystallography determines the exact 3-dimensional positions of atoms in molecules. Structures of molecular complexes in the disciplines of immunology and allergy have revealed the atoms involved in molecular interactions and mechanisms of disease. These complexes include peptides presented by MHC class II molecules, cytokines bound to their receptors, allergen-antibody complexes, and innate immune receptors with their ligands. The information derived from crystallographic studies provides insights into the function of molecules. Allergen function is one of the determinants of environmental exposure, which is essential for IgE sensitization. Proteolytic activity of allergens or their capacity to bind LPSs can also contribute to allergenicity. The atomic positions define the molecular surface that is accessible to antibodies. In turn, this surface determines antibody specificity and cross-reactivity, which are important factors for the selection of allergen panels used for molecular diagnosis and the interpretation of clinical symptoms. This review celebrates the contributions of x-ray crystallography to clinical immunology and allergy, focusing on new molecular perspectives that influence the diagnosis and treatment of allergic diseases.
authors.affiliation: Basic Research, INDOOR Biotechnologies, Charlottesville, Va. Electronic address: apomes@inbio.com.
authors.forename: Anna
authors.initials: A
authors.lastname: Pomés
authors.affiliation: Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC.
authors.forename: Maksymilian
authors.initials: M
authors.lastname: Chruszcz
authors.affiliation: Macromolecular Crystallography Laboratory, National Cancer Institute, Frederick, Md.
authors.forename: Alla
authors.initials: A
authors.lastname: Gustchina
authors.affiliation: Department of Molecular Physiology and Biological Physic, University of Virginia, Charlottesville, Va.
authors.forename: Wladek
authors.initials: W
authors.lastname: Minor
authors.affiliation: Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC.
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Mueller
authors.affiliation: Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC.
authors.forename: Lars C
authors.initials: LC
authors.lastname: Pedersen
authors.affiliation: Macromolecular Crystallography Laboratory, National Cancer Institute, Frederick, Md.
authors.forename: Alexander
authors.initials: A
authors.lastname: Wlodawer
authors.affiliation: Basic Research, INDOOR Biotechnologies, Charlottesville, Va.
authors.forename: Martin D
authors.initials: MD
authors.lastname: Chapman
mesh_terms: D000485:Allergens / Q000737:chemistry* / Q000648:ultrastructure; D000486:Allergy and Immunology / Q000266:history / Q000639:trends*; D000818:Animals; D018360:Crystallography, X-Ray / Q000266:history / Q000706:statistics & numerical data*; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D006967:Hypersensitivity / Q000175:diagnosis / Q000276:immunology*; D007114:Immunization; D007073:Immunoglobulin E / Q000378:metabolism; D008968:Molecular Conformation; D011485:Protein Binding
chemical_list: D000485:Allergens; D007073:Immunoglobulin E
keywords: Allergens; allergy; cross-reactivity; function; structure; x-ray crystallography