title: Crossreactivity and T-cell epitope specificity of Bet v 1-specific T cells suggest the involvement of multiple isoallergens in sensitization to birch pollen.
abstract: BACKGROUND
  Allergen-specific T lymphocytes play an important role in the pathophysiology of atopic disease. Detailed studies of their epitope-specificity and crossreactivity are required for the development of novel approaches for specific immunotherapy.
  
  
  OBJECTIVE
  The aim of the study was to characterize the fine specificity of Bet v 1-specific T cells from allergic donors.
  
  
  METHODS
  Polyclonal T-cell lines (TCL) and T-cell clones (TCC), specific for Bet v 1, the major birch (Betula verrucosa) pollen allergen, were isolated from the peripheral blood of three birch-allergic patients. Their epitope-specificity was studied using overlapping synthetic peptides, and crossreactivity with other tree pollen allergens of the Fagales order was evaluated. In addition, the Bet v 1-specific TCC were studied for their phenotype and cytokine production.
  
  
  RESULTS
  All isolated Bet v 1-specific TCC (19/21 CD4+, 2/21 CD8+) reacted with affinity purified Bet v 1, but showed different reactivities with recombinant Bet v 1 (rBet v 1), and with group 1 allergens from other Fagales species. Epitope mapping of rBet v 1-reactive TCC with synthetic peptides of Bet v 1 showed the presence of four T-cell epitopes. Polyclonal T-cell lines reacted with 13 different peptides, and displayed even broader crossreactivity with group 1 pollen allergens from other Fagales members.
  
  
  CONCLUSIONS
  This study demonstrates that apart from T-cell epitopes of rBet v 1, many other crossreactive or Bet v 1 isoallergen-specific epitopes exist. This indicates that isoallergenic variation plays an important role in the induction of Bet v 1-specific and crossreactive T-cell responsiveness to allergens.
authors.affiliation: ALK ABELLO, Hørsholm, Denmark.
authors.forename: S H
authors.initials: SH
authors.lastname: Sparholt
authors.forename: J N
authors.initials: JN
authors.lastname: Larsen
authors.forename: H
authors.initials: H
authors.lastname: Ipsen
authors.forename: C
authors.initials: C
authors.lastname: Schou
authors.forename: R J
authors.initials: RJ
authors.lastname: van Neerven
mesh_terms: D000485:Allergens / Q000276:immunology*; D000595:Amino Acid Sequence; D052179:Antigens, Plant; D002460:Cell Line / Q000276:immunology; D002999:Clone Cells / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology; D010449:Peptide Mapping; D010940:Plant Proteins / Q000032:analysis / Q000276:immunology*; D011058:Pollen / Q000737:chemistry / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D012680:Sensitivity and Specificity; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology*; D014197:Trees
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D000939:Epitopes; D009842:Oligopeptides; D010940:Plant Proteins; D011994:Recombinant Proteins; C061312:Bet v 1 allergen, Betula; D007073:Immunoglobulin E