| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical College, Asahikawa, Japan;
Department of Pathology, Asahikawa Medical College, Asahikawa, Japan; and
H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, FL 33612
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 1141–156 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-
. 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This study was supported by a grant from the Akiyama Foundation (to H.K.) and by National Institutes of Health Grants R01CA80782 and R01CA103921 (to E.C.).
2 T.N. and H.K. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Toshihiro Nagato, Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical College, Midorigaoka-Higashi 2-1-1-1, Asahikawa 078-8510, Japan; E-mail address: rijun{at}asahikawa-med.ac.jp or Dr. Masatoshi Tateno, Department of Pathology, Asahikawa Medical College, Midorigaoka-Higashi 2-1-1-1, Asahikawa 078-8510, Japan; E-mail address: tateno-m{at}asahikawa-med.ac.jp
4 Abbreviations used in this paper: Treg, regulatory T; GITR, glucocorticoid-induced TNFR; Foxp3, Forkhead Box P3; RAST, radioallergosorbent test; L cell, mouse fibroblasts cell line; r-Bet v 1, recombinant Bet v 1; DC, dendritic cell; 2-M, 2-microglobulin; PADRE, pan DR epitope.
This article has been cited by other articles:
|
|
 |
|
  M. Suzuki, X. Zheng, X. Zhang, M. Li, C. Vladau, T. E. Ichim, H. Sun, L. R. Min, B. Garcia, and W.-P. Min Novel Vaccination for Allergy through Gene Silencing of CD40 Using Small Interfering RNA J. Immunol., June 15, 2008; 180(12): 8461 - 8469. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
