Correlation of sensitizing capacity and T-cell recognition within the Bet v 1 family - 03/07/15
Abstract |
Background |
Bet v 1 is the main sensitizing allergen in birch pollen. Like many other major allergens, it contains an immunodominant T cell–activating region (Bet v 1142-156). Api g 1, the Bet v 1 homolog in celery, lacks the ability to sensitize and is devoid of major T-cell epitopes.
Objective |
We analyzed the T-cell epitopes of Mal d 1, the nonsensitizing Bet v 1 homolog in apple, and assessed possible differences in uptake and antigen processing of Bet v 1, Api g 1, and Mal d 1.
Methods |
For epitope mapping, Mal d 1–specific T-cell lines were stimulated with overlapping synthetic 12-mer peptides. The surface binding, internalization, and intracellular degradation of Bet v 1, Api g 1, and Mal d 1 by antigen-presenting cells were compared by using flow cytometry. All proteins were digested with endolysosomal extracts, and the resulting peptides were identified by means of mass spectrometry. The binding of Bet v 1142-156 and the homologous region in Mal d 1 by HLA class II molecules was analyzed in silico.
Results |
Like Api g 1, Mal d 1 lacked dominant T-cell epitopes. The degree of surface binding and the kinetics of uptake and endolysosomal degradation of Bet v 1, Api g 1, and Mal d 1 were comparable. Endolysosomal degradation of Bet v 1 and Mal d 1 resulted in very similar fragments. The Bet v 1142-156 and Mal d 1141-155 regions showed no striking difference in their binding affinities to the most frequent HLA-DR alleles.
Conclusion |
The sensitizing activity of different Bet v 1 homologs correlates with the presence of immunodominant T-cell epitopes. However, the presence of Bet v 1142-156 is not conferred by differential antigen processing.
Le texte complet de cet article est disponible en PDF.Key words : Allergic sensitization, Bet v 1, birch pollen–associated food allergy, immunodominant T-cell epitope, molecular allergology
Abbreviations used : aa, APC, DC, DOL, FITC, mDC, mdDC, nsLTP, pDC, TCL
Plan
| Supported by the Christian Doppler Research Association, Biomay AG, Austria, and the Austrian Science Fund, projects SFB F4610 and W1212 and W1213. |
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| Disclosure of potential conflict of interest: P. Briza is employed by the University of Salzburg. F. Ferreira is a board member for HAL Allergy (NL), Indoor Biotechnologies, and AllergenOnline; is employed by the University of Salzburg; and has been supported by Austrian Science Funds (FWF). B. Bohle has been supported by Austrian Science Funds and the Christian Doppler Laboratory for Immunomodulation. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 136 - N° 1
P. 151-158 - juillet 2015 Retour au numéro
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