title: T cell epitope immunotherapy ameliorates allergic responses in a murine model of shrimp allergy.
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
  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.
authors.affiliation: School of Life Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
authors.forename: C Y Y
authors.initials: CY
authors.lastname: Wai
authors.affiliation: School of Life Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
authors.forename: N Y H
authors.initials: NY
authors.lastname: Leung
authors.affiliation: Division of Rheumatology/Allergy, School of Medicine, University of California, Davis, CA, 95616, USA.
authors.forename: P S C
authors.initials: PS
authors.lastname: Leung
authors.affiliation: School of Life Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
authors.forename: K H
authors.initials: KH
authors.lastname: Chu
mesh_terms: D000485:Allergens / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D015415:Biomarkers; D016207:Cytokines / Q000378:metabolism; D003888:Desensitization, Immunologic / Q000379:methods; D004195:Disease Models, Animal; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D005512:Food Hypersensitivity / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D051379:Mice; D033561:Penaeidae / Q000276:immunology*; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011506:Proteins / Q000276:immunology; D058408:Th1-Th2 Balance
chemical_list: D000485:Allergens; D015415:Biomarkers; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; C102464:Met e 1 allergen; D010455:Peptides; D011506:Proteins; D007073:Immunoglobulin E
keywords: Met e 1; T cell epitopes; Th1/Th2 balance; allergen-specific immunotherapy; peptide immunotherapy; peripheral tolerance; shellfish