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. 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. [Copyright &y& Elsevier]