Functional analysis of birch pollen allergen Bet v 1-specific regulatory T cells

Toshihiro Nagato, Hiroya Kobayashi, Mitsuru Yanai, Keisuke Sato, Naoko Aoki, Kensuke Oikawa, Shoji Kimura, Yusuke Abe, Esteban Celis, Yasuaki Harabuchi, Masatoshi Tateno

Research output: Contribution to journalArticle

18 Scopus citations

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 1114-156 and Bet v 151-68). 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 1141-156 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-β. 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.

Original languageEnglish (US)
Pages (from-to)1189-1198
Number of pages10
JournalJournal of Immunology
Volume178
Issue number2
DOIs
StatePublished - Jan 15 2007
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Nagato, T., Kobayashi, H., Yanai, M., Sato, K., Aoki, N., Oikawa, K., Kimura, S., Abe, Y., Celis, E., Harabuchi, Y., & Tateno, M. (2007). Functional analysis of birch pollen allergen Bet v 1-specific regulatory T cells. Journal of Immunology, 178(2), 1189-1198. https://doi.org/10.4049/jimmunol.178.2.1189