Allergenic characteristics of a modified peanut allergen

• Published in: Molecular nutrition & food research Vol. 49; no. 10; pp. 963 - 971
• Main Authors: King, Nina, Helm, Ricki, Stanley, J. Steven, Vieths, Stefan, Lüttkopf, Dirk, Hatahet, Lina, Sampson, Hugh, Pons, Laurent, Burks, Wesley, Bannon, Gary A.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.10.2005; WILEY‐VCH Verlag; Wiley-VCH-Verl
• Subjects: 2S Albumins, Plant; Allergens; Allergens - chemistry; Allergens - genetics; Allergens - immunology; Allergy; Amino Acid Sequence; Animals; Antigens, Plant; Arachis hypogaea; Binding Sites; Biological and medical sciences; Cell Line, Tumor; DNA, Complementary; Epitopes - chemistry; Food industries; Fundamental and applied biological sciences. Psychology; General aspects; Glycoproteins - chemistry; Glycoproteins - genetics; Glycoproteins - immunology; Humans; Hypoallergenic; Immunoglobulin E - blood; Immunoglobulin E - immunology; Immunotherapy; Leukemia, Basophilic, Acute; Lymphocyte Activation; Methods of analysis, processing and quality control, regulation, standards; Molecular Sequence Data; Mutagenesis, Site-Directed; Peanut; Peanut Hypersensitivity - immunology; Plant Proteins - chemistry; Plant Proteins - genetics; Plant Proteins - immunology; Polymerase Chain Reaction; Rats; Recombinant Proteins - immunology; T-Lymphocytes - immunology; Immunopathology; Allergy; Peanut; Allergens; Leguminosae; Dicotyledones; Immunotherapy; Angiospermae; Hypoallergenic; Arachis hypogaea; Spermatophyta; Allergen
• ISSN: 1613-4125; 1613-4133; 1521-3803
• DOI: 10.1002/mnfr.200500073

Attempts to treat peanut allergy using traditional methods of allergen desensitization are accompanied by a high risk of anaphylaxis. The aim of this study was to determine if modifications to the IgE‐binding epitopes of a major peanut allergen would result in a safer immunotherapeutic agent for the treatment of peanut‐allergic patients. IgE‐binding epitopes on the Ara h 2 allergen were modified, and modified Ara h 2 (mAra h 2) protein was produced. Wild‐type (wAra h 2) and mAra h 2 proteins were analyzed for their ability to interact with T‐cells, their ability to bind IgE, and their ability to release mediators from a passively sensitized RBL‐2H3 cell line. Multiple T‐cell epitopes were identified on the major peanut allergen, Ara h 2. Ara h 2 amino acid regions 11–35, 86–125, and 121–155 contained the majority of peptides that interact with T‐cells from most patients. The wAra h 2 and mAra h 2 proteins stimulated proliferation of T‐cells from peanut‐allergic patients to similar levels. In contrast, the mAra h 2 protein exhibited greatly reduced IgE‐binding capacity compared to the wild‐type allergen. In addition, the modified allergen released significantly lower amounts of β‐hexosaminidase, a marker for IgE‐mediated RBL‐2H3 degranulation, compared to the wild‐type allergen.