Ara h 1 CD4+ T cell epitope-based peptides: candidates for a peanut allergy therapeutic.
Clin Exp Allergy
; 43(6): 684-97, 2013 Jun.
Article
en En
| MEDLINE
| ID: mdl-23711131
ABSTRACT
BACKGROUND:
Peanut allergy is a life-threatening condition; there is currently no cure. While whole allergen extracts are used for specific immunotherapy for many allergies, they can cause severe reactions and even fatalities in peanut allergy.OBJECTIVE:
To identify short, HLA-degenerate CD4(+) T cell epitope-based peptides of the major peanut allergen Ara h 1 that target allergen-specific T cells without causing IgE-mediated inflammatory cell activation, as candidates for safe peanut-specific immunotherapy.METHODS:
Ara h 1-specific CD4(+) T cell lines (TCL) were generated from peripheral blood mononuclear cells (PBMC) of peanut-allergic subjects using CFSE-based methodology. T cell epitopes were identified using CFSE and thymidine-based proliferation assays. Epitope HLA-restriction was investigated using blocking antibodies, HLA-genotyping and epitope prediction algorithms. Functional peanut-specific IgE reactivity to peptides was assessed by basophil activation assay.RESULTS:
A total of 145 Ara h 1-specific TCL were generated from 18 HLA-diverse peanut-allergic subjects. The TCL recognized 20-mer peptides throughout Ara h 1. Nine 20-mers containing the most frequently recognized epitopes were selected and their recognition confirmed in 18 additional peanut-allergic subjects. Ten core epitopes were mapped within these 20-mers. These were HLA-DQ and/or HLA-DR restricted, with each presented on at least two different HLA-molecules. Seven short (≤ 20 aa) non-basophil-reactive peptides encompassing all core epitopes were designed and validated in peanut-allergic donor PBMC T cell assays. CONCLUSIONS AND CLINICAL RELEVANCE Short CD4(+) T cell epitope-based Ara h 1 peptides were identified as novel candidates for a safe, T cell targeted peanut-specific immunotherapy for HLA-diverse populations.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Péptidos
/
Proteínas de Plantas
/
Glicoproteínas
/
Linfocitos T CD4-Positivos
/
Epítopos de Linfocito T
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Hipersensibilidad al Cacahuete
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Antígenos de Plantas
Límite:
Humans
Idioma:
En
Revista:
Clin Exp Allergy
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Australia