title: Spatial clustering of the IgE epitopes on the major timothy grass pollen allergen Phl p 1: importance for allergenic activity.
abstract: BACKGROUND
  The major timothy grass pollen allergen Phl p 1 is one of the most potent and frequently recognized environmental allergens.
  
  
  OBJECTIVE
  We sought to study at a molecular and structural level the IgE recognition of Phl p 1 and its relation to allergenic activity.
  
  
  METHODS
  Monoclonal human IgE antibody fragments specific for Phl p 1 and group 1 allergens from various grasses were isolated from a combinatorial library made of lymphocytes from patients with grass pollen allergy. Recombinant Phl p 1 fragments and the 3-dimensional structure of Phl p 1 were used to localize the major binding site for the IgE antibodies. A rPhl p 1 fragment containing this binding site was expressed in Escherichia coli, purified, and tested for IgE reactivity and allergenic activity with sera and basophils from patients with grass pollen allergy.
  
  
  RESULTS
  Monoclonal antibodies, as well as polyclonal serum IgE, from patients with grass pollen allergy defined a C-terminal fragment of Phl p 1 that represents a sterically oriented portion on the Phl p 1 structure. This Phl p 1 portion bound most of the allergen-specific IgE antibodies and contained the majority of the allergenic activity of Phl p 1.
  
  
  CONCLUSIONS
  IgE recognition of spatially clustered epitopes on allergens might be a general factor determining their allergenic activity.
  
  
  CONCLUSIONS
  Geographic distribution of IgE epitopes on an allergen might influence its allergenic activity and hence explain discrepancies between diagnostic test results based on IgE serology and provocation testing. It might also form a basis for the development of low allergenic vaccines.
authors.affiliation: Department of Pathophysiology, Center for Physiology and Pathophysiology, Medical University of Vienna, Austria.
authors.forename: Sabine
authors.initials: S
authors.lastname: Flicker
authors.forename: Peter
authors.initials: P
authors.lastname: Steinberger
authors.forename: Tanja
authors.initials: T
authors.lastname: Ball
authors.forename: Maria-Theresa
authors.initials: MT
authors.lastname: Krauth
authors.forename: Petra
authors.initials: P
authors.lastname: Verdino
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
authors.forename: Steve
authors.initials: S
authors.lastname: Almo
authors.forename: Rudolf
authors.initials: R
authors.lastname: Valenta
mesh_terms: D000485:Allergens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001665:Binding Sites / Q000276:immunology; D003429:Cross Reactions; D018604:Epitope Mapping; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology* / Q000378:metabolism; D007073:Immunoglobulin E / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D031784:Phleum / Q000276:immunology*; D010865:Pilot Projects; D010940:Plant Proteins / Q000235:genetics / Q000276:immunology*; D011058:Pollen / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D010940:Plant Proteins; C090396:PHLPI protein, Phleum pratense; D007073:Immunoglobulin E