title: Correlation of sensitizing capacity and T-cell recognition within the Bet v 1 family.
abstract: BACKGROUND
  Bet v 1 is the main sensitizing allergen in birch pollen. Like many other major allergens, it contains an immunodominant T cell-activating region (Bet v 1142-156). Api g 1, the Bet v 1 homolog in celery, lacks the ability to sensitize and is devoid of major T-cell epitopes.
  
  
  OBJECTIVE
  We analyzed the T-cell epitopes of Mal d 1, the nonsensitizing Bet v 1 homolog in apple, and assessed possible differences in uptake and antigen processing of Bet v 1, Api g 1, and Mal d 1.
  
  
  METHODS
  For epitope mapping, Mal d 1-specific T-cell lines were stimulated with overlapping synthetic 12-mer peptides. The surface binding, internalization, and intracellular degradation of Bet v 1, Api g 1, and Mal d 1 by antigen-presenting cells were compared by using flow cytometry. All proteins were digested with endolysosomal extracts, and the resulting peptides were identified by means of mass spectrometry. The binding of Bet v 1142-156 and the homologous region in Mal d 1 by HLA class II molecules was analyzed in silico.
  
  
  RESULTS
  Like Api g 1, Mal d 1 lacked dominant T-cell epitopes. The degree of surface binding and the kinetics of uptake and endolysosomal degradation of Bet v 1, Api g 1, and Mal d 1 were comparable. Endolysosomal degradation of Bet v 1 and Mal d 1 resulted in very similar fragments. The Bet v 1142-156 and Mal d 1141-155 regions showed no striking difference in their binding affinities to the most frequent HLA-DR alleles.
  
  
  CONCLUSIONS
  The sensitizing activity of different Bet v 1 homologs correlates with the presence of immunodominant T-cell epitopes. However, the presence of Bet v 1142-156 is not conferred by differential antigen processing.
authors: Christian Doppler Laboratory for Immunomodulation, Medical University of Vienna, Vienna, Austria; Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria.
authors: Claudia
authors: C
authors: Kitzmüller
authors: Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria.
authors: Nora
authors: N
authors: Zulehner
authors: Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
authors: Anargyros
authors: A
authors: Roulias
authors: Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
authors: Peter
authors: P
authors: Briza
authors: Department of Molecular Biology, University of Salzburg, Salzburg, Austria; Christian Doppler Laboratory for Allergy Diagnosis and Therapy, University of Salzburg, Salzburg, Austria.
authors: Fatima
authors: F
authors: Ferreira
authors: Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria.
authors: Ingrid
authors: I
authors: Faé
authors: Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria.
authors: Gottfried F
authors: GF
authors: Fischer
authors: Christian Doppler Laboratory for Immunomodulation, Medical University of Vienna, Vienna, Austria; Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria. Electronic address: barbara.bohle@meduniwien.ac.at.
authors: Barbara
authors: B
authors: Bohle
mesh_terms: D017951:Antigen Presentation; D052179:Antigens, Plant / Q000737:chemistry / Q000276:immunology*; D000077102:Apium; D029662:Betula; D002460:Cell Line; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007114:Immunization; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology; D008213:Lymphocyte Activation; D027845:Malus; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D010940:Plant Proteins / Q000737:chemistry / Q000276:immunology; D011485:Protein Binding; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D052179:Antigens, Plant; C096695:Api g 1 protein, Apium graveolens; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D016056:Immunodominant Epitopes; C095551:MALD1 protein, Malus domestica; D010446:Peptide Fragments; D010940:Plant Proteins; C061312:Bet v 1 allergen, Betula
keywords: Allergic sensitization; Bet v 1; birch pollen–associated food allergy; immunodominant T-cell epitope; molecular allergology