Relationships between T cell and IgE/IgG4 epitopes of the Anisakis simplex major allergen Ani s 1

BACKGROUND: Anisakiasis is a global disease caused by the consumption of raw or lightly cooked fish parasitized with third-stage Anisakis larvae. Anisakis simplex allergens may cause severe allergic reactions including angio-oedema, urticaria and anaphylaxis. Approximately 80% of allergic patients have allergen-specific IgE against Ani s 1, and the diagnostic value of testing for antibodies to Ani s 1 has been extensively demonstrated. However, no previous studies have investigated the molecular aspects of the allergic response to Ani s 1. Knowledge of allergen-specific T cell and B cell (IgE and IgG4) epitopes is important for elucidating the immunological mechanisms underlying allergic responses, and for understanding why particular proteins behave as allergens. OBJECTIVE: To elucidate the main T cell- and B cell (IgE and IgG4)- binding regions of Ani s 1. METHODS: T cell epitopes were identified by peptide proliferation assays using T cell lines derived from peripheral blood mononuclear cells of 11 patients with Anisakis allergy, and IgE and IgG4 epitopes were identified by microarray immunoassay using sera from a different group of 11 patients with Anisakis allergy. RESULTS: Several T cell epitopes of Ani s 1 were identified, of which Ani s 1145-156 , Ani s 1151-162 and Ani s 1163-171 located at the C-terminal end of the protein were the most relevant. IgE and IgG4 recognized largely the same peptides, including Ani s 122-41 , Ani s 125-44 , Ani s 127-47 , Ani s 137-56 and Ani s 194-113 . CONCLUSIONS AND CLINICAL RELEVANCE: This is the first report describing the T cell epitopes of an important allergen of A. simplex, and the first B cell epitope study of this allergen in the Spanish population. This information can help to elucidate the mechanisms underlying the allergic response to Ani s 1, potentially leading to therapeutic and diagnostic advances.