Oral immunotherapy with immunodominant T‐cell epitope peptides alleviates allergic reactions in a Balb/c mouse model of egg allergy

Abstract

Allergen-specific T-cell epitopes are obvious targets for immunotherapeutic interventions in allergic disease. T-cell epitope peptides given orally may provide a practical way of inducing tolerance and preventing allergy. This study investigates oral immunotherapy (OIT) with T-cell epitope peptides of the dominant egg-white allergen ovomucoid (Ovm) in a Balb/c mouse model of egg allergy. Groups of mice were orally sensitized to Ovm and subsequently administered Ovm T-cell epitopes [single peptide 157-171 (SP) or multiple peptide (157-171)(3) (MP)], followed by oral challenge with Ovm. Outcomes post oral challenge were measured as clinical signs, serum histamine, antibody activity (IgG, IgE, IgG1, IgG2, IgA), cytokines (IL-4, IFN-γ, IL-12p70, IL-10, TGF-β, and IL-17), and T regulatory cells (Tregs). Clinical signs were less frequent in both SP and MP groups (P ≤ 0.05). Specific IgE was less and IgA was more in both groups; however, SP-treated mice had less histamine and IgG1 and more IgG2-related antibodies indicating a bias toward the type-1 response (P ≤ 0.05). Concentration of type-2 cytokine interleukin-4 (IL-4) was significantly less in both groups and IL-12p70 and IL-10 were more in SP-treated mice (P ≤ 0.001). Interferon-γ, IL-17, and TGF-β did not differ significantly. There was significant increase in the percentage of CD4+FOXP3+ and CD4+CD25+ cells in the SP group, indicating the significant role of Tregs in immune regulation. In summary, we demonstrated that OIT with SP and MP comprising the immunodominant regions of Ovm was safe and significantly reduced subsequent frequency of allergy to Ovm, and validated potential use of Ovm T-cell epitope as an immunoregulator.