Efficient induction of CD25(- )iTreg by co-immunization requires strongly antigenic epitopes for T cells

BACKGROUND: We previously showed that co-immunization with a protein antigen and a DNA vaccine coding for the same antigen induces CD40(low )IL-10(high )tolerogenic DCs, which in turn stimulates the expansion of antigen-specific CD4(+)CD25(-)Foxp3(+ )regulatory T cells (CD25(- )iTreg). However, it was unclear how to choose the antigen sequence to maximize tolerogenic antigen presentation and, consequently, CD25(- )iTreg induction. RESULTS: In the present study, we demonstrated the requirement of highly antigenic epitopes for CD25(- )iTreg induction. Firstly, we showed that the induction of CD25(- )iTreg by tolerogenic DC can be blocked by anti-MHC-II antibody. Next, both the number and the suppressive activity of CD25(- )iTreg correlated positively with the overt antigenicity of an epitope to activate T cells. Finally, in a mouse model of dermatitis, highly antigenic epitopes derived from a flea allergen not only induced more CD25(- )iTreg, but also more effectively prevented allergenic reaction to the allergen than did weakly antigenic epitopes. CONCLUSIONS: Our data thus indicate that efficient induction of CD25(- )iTreg requires highly antigenic peptide epitopes. This finding suggests that highly antigenic epitopes should be used for efficient induction of CD25(- )iTreg for clinical applications such as flea allergic dermatitis.