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


CONCLUSIONS
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.
Christian Doppler Laboratory for Allergy Diagnosis and Therapy, Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
Sonja
S
Mutschlechner
Matthias
M
Egger
Peter
P
Briza
Michael
M
Wallner
Peter
P
Lackner
Anette
A
Karle
Anne B
AB
Vogt
Gottfried F
GF
Fischer
Barbara
B
Bohle
Fatima
F
Ferreira
D017951:Antigen Presentation / Q000276:immunology*; D052179:Antigens, Plant / Q000276:immunology / Q000378:metabolism*; D029662:Betula / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008247:Lysosomes / Q000378:metabolism; D013058:Mass Spectrometry; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D011058:Pollen / Q000276:immunology / Q000378:metabolism; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000378:metabolism*
D052179:Antigens, Plant; D018984:Epitopes, T-Lymphocyte; D010455:Peptides