The purpose of this study was to evaluate whether the vaccination of naked plasmid DNA encoding only T-cell epitopes suppresses the allergic reaction as effectively as naked DNA encoding whole segment of allergen. We immunized mice with naked plasmid DNA encoding the five classes of murine T-cell epitopes on Der p1 and Der p2 three times at weekly intervals via an intramuscular injection. Control mice were injected with the pcDNA 3.1 blank vectors. After 3 weeks, mice were actively sensitized twice and allowed to inhale the Der p extracts intranasally six times at weekly intervals. The vaccinated mice showed a significant attenuated induction of Der p-specific immunoglobulin E synthesis compared to controls. Analysis of the cytokines profile after Der p stimulation of the lymph node cells revealed that the level of the mRNA expression of the interferon-γ gene was higher in the vaccinated mice than in the controls. Histologic studies showed much reduced infiltration of inflammatory cells in lung tissue of the gene-vaccinated mice than the controls. Thus, gene therapy using T-cell epitope encoding DNA presenting is an ideal way of combating allergic disease in the future.