title: Functional analysis of birch pollen allergen Bet v 1-specific regulatory T cells.
abstract: Allergen-specific immunotherapy using peptides is an efficient treatment for allergic diseases. Recent studies suggest that the induction of CD4+ regulatory T (Treg) cells might be associated with the suppression of allergic responses in patients after allergen-specific immunotherapy. Our aim was to identify MHC class II promiscuous T cell epitopes for the birch pollen allergen Bet v 1 capable of stimulating Treg cells with the purpose of inhibiting allergic responses. Ag-reactive CD4+ T cell clones were generated from patients with birch pollen allergy and healthy volunteers by in vitro vaccination of PBMC using Bet v 1 synthetic peptides. Several CD4+ T cell clones were induced by using 2 synthetic peptides (Bet v 1(141-156) and Bet v 1(51-68)). Peptide-reactive CD4+ T cells recognized recombinant Bet v 1 protein, indicating that these peptides are produced by the MHC class II Ag processing pathway. Peptide Bet v 1(141-156) appears to be a highly MHC promiscuous epitope since T cell responses restricted by numerous MHC class II molecules (DR4, DR9, DR11, DR15, and DR53) were observed. Two of these clones functioned as typical Treg cells (expressed CD25, GITR, and Foxp3 and suppressed the proliferation and IL-2 secretion of other CD4+ T cells). Notably, the suppressive activity of these Treg cells required cell-cell contact and was not mediated through soluble IL-10 or TGF-beta. The identified promiscuous MHC class II epitope capable of inducing suppressive Treg responses may have important implication for the development of peptide-based Ag-specific immunotherapy to birch pollen allergy.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical College, Midorigaoka-Higashi 2-1-1-1, Asahikawa 078-8510, Japan. rijun@asahikawa-med.ac.jp
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nagato
authors.forename: Hiroya
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Yanai
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sato
authors.forename: Naoko
authors.initials: N
authors.lastname: Aoki
authors.forename: Kensuke
authors.initials: K
authors.lastname: Oikawa
authors.forename: Shoji
authors.initials: S
authors.lastname: Kimura
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Abe
authors.forename: Esteban
authors.initials: E
authors.lastname: Celis
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Harabuchi
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Tateno
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D029662:Betula / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D010641:Phenotype; D010940:Plant Proteins / Q000276:immunology*; D011058:Pollen / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000485:Allergens; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D010940:Plant Proteins