MODULATION OF THE ALLERGIC IMMUNE-RESPONSE IN BALB C MICE BY SUBCUTANEOUS INJECTION OF HIGH-DOSES OF THE DOMINANT T-CELL EPITOPE FROM THE MAJOR BIRCH POLLEN ALLERGEN-BET-V-1/

Several in vitro and in vivo studies indicate that application of high doses of dominant T cell epitopes can induce a state of antigen-speci fic non-responsiveness (anergy). In the present study, we developed a murine model of an allergic immune response to Bet v 1, the major birc h pollen allergen. Mice were sensitized by injection of rBet v 1 and t he allergic state was proven by the presence of allergen-specific IgE and positive immediate-type skin tests to Bet v 1. In epitope mapping experiments, an immunodominant T cell epitope of Bet v 1 in BALB/c mic e was identified by the use of overlapping peptides. This peptide (BV1 39) was subsequently employed for treatment. Two tolerization protocol s were used: in one approach, the peptide was administered to naive mi ce before immunization (group BV139-S), in the second, already sensiti zed mice were treated (S-BV139). The results demonstrated that adminis tering high doses of the dominant T cell epitope of Bet v 1 profoundly diminished T cell proliferation to the peptide in the BV139-S group, and to the peptide as well as to the whole protein in the S-BV139 grou p. Skin test reactivity to Bet v 1 was reduced in the BV139-S group. H owever, no differences in terms of specific antibody production betwee n treated and untreated mice could be observed. This study provides ev idence that administration of dominant T cell epitopes can down-regula te the allergen-specific T cell response. Proceeding on the assumption that the T lymphocyte response to allergens is crucial for the induct ion and maintenance of the allergic disease, a modulation of the immun e response to allergens by treatment with T cell epitope peptides coul d represent a promising concept for immunotherapy in the future.