title: Dissection of the IgE and T-cell recognition of the major group 5 grass pollen allergen Phl p 5.
abstract: BACKGROUND
  The major timothy grass pollen allergen Phl p 5 belongs to the most potent allergens involved in hay fever and asthma.
  
  
  OBJECTIVE
  This study characterized immune-dominant IgE- and T-cell-recognition sites of Phl p 5.
  
  
  METHODS
  Seven peptides, P1 to P7 with a length of 31 to 38 amino acids that spanned the Phl p 5 sequence, were synthesized, characterized by circular dichroism spectroscopy, and tested for IgE reactivity, basophil activation, and T-cell reactivity. Carrier-bound peptides were studied for their ability to induce IgG antibodies in rabbits which recognize Phl p 5 or cross-reactive allergens from different grass species. Peptide-specific antibodies were tested for the capability to inhibit IgE reactivity to Phl p 5 and allergen-induced basophil activation of patients with allergy.
  
  
  RESULTS
  The peptides exhibited no secondary structure and showed no IgE reactivity or relevant allergenic activity, indicating that Phl p 5 IgE epitopes are conformational. Except for P3, peptide-specific IgG antibodies blocked IgE binding to Phl p 5 of patients with allergy and cross-reacted with temperate grasses. IgE inhibition experiments and molecular modeling identified several clustered conformational IgE epitopes on the N- as well as C-terminal domain of Phl p 5. P4, which stimulated the strongest T-cell and cytokine responses in patients, was not part of the major IgE-reactive regions.
  
  
  CONCLUSIONS
  Our study shows an interesting dissociation of the major IgE- and T-cell-reactive domains in Phl p 5 which provides a basis for the development of novel forms of immunotherapy that selectively target IgE or T-cell responses.
authors.affiliation: Christian Doppler Laboratory for Allergy Research, Medical University of Vienna, Vienna, Austria; Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Margarete
authors.initials: M
authors.lastname: Focke-Tejkl
authors.affiliation: Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Raffaela
authors.initials: R
authors.lastname: Campana
authors.affiliation: Christian Doppler Laboratory for Allergy Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Renate
authors.initials: R
authors.lastname: Reininger
authors.affiliation: Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Lupinek
authors.affiliation: Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Blatt
authors.affiliation: Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
authors.affiliation: Institute of Molecular Biosciences, University of Graz, Graz, Austria.
authors.forename: Tea
authors.initials: T
authors.lastname: Pavkov-Keller
authors.affiliation: Institute of Molecular Biosciences, University of Graz, Graz, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Keller
authors.affiliation: Christian Doppler Laboratory for Allergy Research, Medical University of Vienna, Vienna, Austria; Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria. Electronic address: rudolf.valenta@meduniwien.ac.at.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Valenta
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001491:Basophils / Q000502:physiology; D002648:Child; D003429:Cross Reactions; D016207:Cytokines / Q000096:biosynthesis; D018604:Epitope Mapping; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000737:chemistry / Q000276:immunology*; D017433:Protein Structure, Secondary; D011817:Rabbits; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016207:Cytokines; C076049:Phl p V protein, Phleum pratense; D010940:Plant Proteins; D007073:Immunoglobulin E
keywords: Allergy; epitopes; grass pollen allergen; peptides