Peanut T-cell epitope discovery: Ara h 1 - 03/06/16
Abstract |
Background |
Identification of potential T-cell epitopes in the peanut major allergens is essential for development of peptide-based immunotherapy. Traditional methods of T-cell epitope discovery use overlapping short peptides spanning the full length of the protein in T-cell proliferation assays. Because large proteins, such as Ara h 1, require a large number of peptides, this limits screening to a small number of allergic subject–derived T-cell lines.
Objective |
We sought to identify candidate peptides of Ara h 1 that display promiscuous binding to MHC class II and induce TH2 cytokine production by T cells.
Methods |
In silico MHC class II binding prediction was performed with NetMHCIIpan 2.0 (peptide length, 15; 1-mer offset) and the most abundant class II alleles in the North American population and with an in vitro MHC class II peptide reporter assay performed in parallel, which used synthetic 15-mer peptides offset by 5 mer spanning the protein. High-resolution MHC class II typing and a T-cell proliferation assay using preselected peptides were performed with PBMCs from 98 subjects with peanut allergy and 14 healthy control subjects. IL-4, IL-13, IL-5, IFN-γ, and TNF-α levels were measured in culture supernatants.
Results |
Thirty-six Ara h 1 peptides were identified by using in silico predictions and MHC class II binding assays. In combination with T-cell proliferation and cytokines secreted in T-cell assays, we have identified 4 vaccine candidate Ara h 1 peptides.
Conclusions |
Preselection of peptides by using in silico and in vitro approaches in combination with conventional methods appears to be an effective strategy for identifying peanut T-cell peptide vaccine candidates.
Le texte complet de cet article est disponible en PDF.Key words : Ara h 1, peanut, food allergy, peptide epitope
Abbreviations used : CPE, CV, kUA, OIT
Plan
| Supported by the David H. and Julia Koch Research Program in Food Allergy Therapeutics at the Jaffe Food Allergy Institute, Mount Sinai School of Medicine. |
|
| Disclosure of potential conflict of interest: J. Lieberman has received a grant from the American Academy of Allergy, Asthma & Immunology (AAAAI)/Jaffe Fellowship Grant; is an Associate Editor and Editorial Board member for the Annals of Allergy, Asthma, and Immunology; and has received travel support from CSL Behring. H. A. Sampson has received grants from the National Institute of Allergy and Infectious Diseases and Food Allergy and Research Education; has consultant arrangements with Danone Scientific Advisory Board, Genentech/Novartis, Sanofi, and Allertein Therapeutics; has received royalties from UpToDate and Elsevier; has stock/stock options with Allertein Therapeutics and DBV Therapeutics; and has received honorarium for being chair of the PhARF Selection Committee from Thermo Fisher Scientific. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 137 - N° 6
P. 1764 - juin 2016 Retour au numéro
Article précédent
- The component-specific to total IgE ratios do not improve peanut and hazelnut allergy diagnoses
- Linus Grabenhenrich, Lars Lange, Magdalena Härtl, Birgit Kalb, Mandy Ziegert, Antje Finger, Neda Harandi, Ruppert Schlags, Monika Gappa, Letizia Puzzo, Volker Stephan, Thomas Heigele, Susanne Büsing, Hagen Ott, Bodo Niggemann, Kirsten Beyer
- A call to improve standards for reporting of diagnostic test research in allergy
- Corinne A. Keet
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?