T cell epitope immunotherapy ameliorates allergic responses in a murine model of shrimp allergy

• Published in: Clinical and experimental allergy 2016-03, Vol.46 (3), p.491-503
• Main Authors: Wai, C. Y. Y., Leung, N. Y. H., Leung, P. S. C., Chu, K. H.
• Format: Article
• Language: English
• Subjects: allergen-specific immunotherapy; Allergens - immunology; Amino Acid Sequence; Animals; Antibody Specificity - immunology; Biomarkers; Cytokines - metabolism; Decapoda; Desensitization, Immunologic - methods; Disease Models, Animal; Epitope Mapping; Epitopes, T-Lymphocyte - chemistry; Epitopes, T-Lymphocyte - immunology; Food Hypersensitivity - immunology; Food Hypersensitivity - therapy; Humans; Immunization; Immunoglobulin E - blood; Immunoglobulin E - immunology; Immunoglobulin G - blood; Immunoglobulin G - immunology; Met e 1; Metapenaeus ensis; Mice; Penaeidae - immunology; peptide immunotherapy; Peptides - chemistry; Peptides - immunology; peripheral tolerance; Proteins - immunology; shellfish; T cell epitopes; Th1-Th2 Balance
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/cea.12684

Summary Background Shellfish allergy is one of the most common food hypersensitivities worldwide but allergen‐specific immunotherapy for shellfish allergy is not yet available. We believe that T cell peptide‐based immunotherapy holds the potential for modulating allergic responses without IgE cross‐linking. Objective We sought to identify the immunodominant T cell epitopes of tropomyosin, the major shrimp allergen of Metapenaeus ensis (Met e 1), and to evaluate their therapeutic effects in a Balb/c mouse model of Met e 1 hypersensitivity. Methods T cell epitopes of Met e 1 were first identified based on the proliferation and cytokine responses of splenocytes isolated from Met e 1‐sensitized Balb/c mice upon stimulation by 18 synthetic peptides that span the full‐length Met e 1. The immunodominant T cell peptides identified were then fed orally to Met e 1‐sensitized Balb/c mice twice a week for four weeks. Allergic responses, serological antibody levels, intestinal histology and systemic and local cytokine profiles were compared between the treated and the untreated groups. Results Six major Met e 1 T cell epitopes were identified. Mice treated with the T cell epitope peptide mixture demonstrated an amelioration of systemic allergic symptoms and a significant reduction in Th2‐associated antibody and cytokine responses. These benefits were accompanied by a shift to a balanced Th1/Th2 response, induction of IgG2a antibodies possessing in vitro and in vivo blocking activities and the induction of regulatory T cell responses. Conclusions and Clinical Relevance T cell epitope‐based oral immunotherapy is effective in reducing allergic responses towards shrimp tropomyosin. This is a novel strategy for clinical management of shellfish allergy and is a model for mechanistic studies of oral immunotherapy.