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International Immunology Advance Access published online on October 12, 2005
International Immunology, doi:10.1093/intimm/dxh332
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© The Japanese Society for Immunology. 2005. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Received March 21, 2005
Accepted September 14, 2005

Article

Immunomodulatory potential of heteroclitic analogs of the dominant T-cell epitope of lipocalin allergen Bos d 2 on specific T cells

Tuure Kinnunen 1*, William W. Kwok 2, Ale Närvänen 3, Marja Rytkönen-Nissinen 1, Anu Immonen 1, Soili Saarelainen 1, Antti Taivainen 4, and Tuomas Virtanen 1

1 Department of Clinical Microbiology, University of Kuopio, PO Box 1627, FIN-70211 Kuopio, Finland
2 Benaroya Research Institute at Virginia Mason, Seattle, WA, USA
3 Department of Chemistry, University of Kuopio, Finland
4 Department of Pulmonary Diseases, Kuopio University Hospital, Kuopio, Finland

* To whom correspondence should be addressed.
Tuure Kinnunen, E-mail: ttkinnun{at}hytti.uku.fi


  Abstract

Peptide-based allergen immunotherapy is a novel alternative for conventional allergen immunotherapy. Here, we have characterized the immunomodulatory potential of heteroclitic peptide analogs of the immunodominant epitope of lipocalin allergen Bos d 2 on specific human T-cell clones. The TCR affinity of Bos d 2-specific T-cell clones for the natural peptide ligand and its heteroclitic analogs was assessed with fluorescent-labeled MHC class II tetramers. The activation and cytokine production of the clones were analyzed upon stimulation with the different ligands. Moreover, the capacity of the heteroclitic analogs to induce hyporesponsiveness and cell death was examined. The T-cell clones F1-9 and K3-2 bound MHC class II tetramers loaded with the heteroclitic peptide analogs of the immunodominant epitope of Bos d 2 with increased affinity. At similar peptide concentrations, stimulation of the clones with the heteroclitic analogs favored increased IFN-{gamma}/IL-4 and IFN-{gamma}/IL-5 ratios in comparison with stimulation with the natural peptide ligand. Moreover, the T-cell clones stimulated with the heteroclitic analogs exhibited an increased susceptibility to cell death or hyporesponsiveness upon re-stimulation. Our results suggest that heteroclitic analogs of a T-cell epitope of an allergen may enhance the efficacy of peptide-based allergen immunotherapy.

Keywords: allergy; immunotherapy; peptide; T lymphocyte; tetramer.
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