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J Allergy Clin Immunol. 2010 Mar;125(3):711-8, 718.e1-718.e2. doi: 10.1016/j.jaci.2009.10.052. Epub 2010 Feb 4.

Naturally processed T cell-activating peptides of the major birch pollen allergen.

Author information

1
Christian Doppler Laboratory for Allergy Diagnosis and Therapy, Department of Molecular Biology, University of Salzburg, Salzburg, Austria.

Abstract

BACKGROUND:

Although antigen processing and presentation of allergens to CD4(+)T lymphocytes are key events in the pathophysiology of allergic disorders, they still remain poorly understood.

OBJECTIVE:

To investigate allergen processing and presentation by dendritic cells using the major birch pollen allergen Bet v 1 as a model.

METHODS:

Endolysosomal extracts of dendritic cells derived from patients with birch pollen allergy were used to digest Bet v 1. Dendritic cells were pulsed with Bet v 1, and peptides were eluted from MHC class II molecules. Peptides obtained by either approach were sequenced by tandem mass spectrometry. Bet v 1-specific T-cell cultures were stimulated with HLA-DR-eluted Bet v 1-derived peptides. Bet v 1-specific T-cell lines were generated from each patient and analyzed for epitope recognition.

RESULTS:

A high proportion of Bet v 1 remained intact for a long period of endolysosomal degradation. The peptides that appeared early in the degradation process contained frequently recognized T-cell epitopes. Bet v 1-derived peptides eluted from MHC class II molecules corresponded to those generated by endolysosomal degradation, matched known T-cell epitopes, and showed T cell-activating capacity. The Bet v 1-specific T-cell line of each individual harbored T cells reactive with peptides located within the MHC class II-eluted Bet v 1-derived sequences demonstrating their occurrence in vivo.

CONCLUSION:

We report for the first time how epitopes of allergens are generated and selected for presentation to T lymphocytes. The limited susceptibility of Bet v 1 to endolysosomal processing might contribute to its high allergenic potential.

PMID:
20132976
DOI:
10.1016/j.jaci.2009.10.052
[Indexed for MEDLINE]

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