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

C. Y Y Wai, N. Y H Leung, Patrick S Leung, K. H. Chu

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)491-503
Number of pages13
JournalClinical and Experimental Allergy
Volume46
Issue number3
DOIs
StatePublished - Mar 1 2016

Keywords

  • Allergen-specific immunotherapy
  • Met e 1
  • Peptide immunotherapy
  • Peripheral tolerance
  • Shellfish
  • T cell epitopes
  • Th1/Th2 balance

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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