Effects of orally administered immunodominant T-cell epitope peptides on cow's milk protein allergy in a mouse model

• Effect of 2 epitopes of β-lactoglobulin on oral tolerance development was studied.
• Allergy related clinical signs were alleviated in peptide treated mice.
• Allergy improving effect was not through induction of regulatory T cells.

Immunodominant T-cell epitopes have been reported to induce oral tolerance against egg and pollen allergy. However, whether immunodominant T-cell epitopes have effects on cow's milk allergy is unknown. In this study, two T-cell dominant epitopes of β-lactoglobulin (BLG) were used in pre-sensitized Balb/c mice. Female mice of 3 weeks old were randomly assigned to four experimental groups (n = 18/group). Mice were intraperitoneally (i.p.) sensitized with 3 weekly doses of BLG as well as alum for 3 weeks starting at 4 weeks of age. One week after the final sensitization, mice were gavaged with T-cell dominant peptides for 4 weeks (1 mg/mouse/d and 3d/week). After mice were orally challenged with BLG, clinical and immunological parameters were examined. Compared to untreated control mice, both peptide treated groups had lower hypersensitivity scores with unchanged rectal temperatures, but had similar BLG-specific serum immunoglobulin levels and Treg cell populations. The two T-cell dominant peptides used in our therapeutic study failed to induce CD25+ Foxp3+ regulatory T cells and reduce allergen-specific systemic markers in BLG-sensitized mice. However, clinical signs for allergic reactions were alleviated in peptide treated mice. Further studies that focus not only on Treg-mediated tolerance but also on IgG, B cells and other T-cell assisted tolerance development mechanisms are required to elucidate the allergy improving effect of these peptides.