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-specific non-responsiveness (anergy). In the present study, we developed a murine model of an allergic immune response to Bet v 1, the major birch pollen allergen. Mice were sensitized by injection of rBet v 1 and the 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 mice was identified by the use of overlapping peptides. This peptide (BV 139) was subsequently employed for treatment. Two tolerization protocols were used: in one approach, the peptide was administered to naive mice before immunization (group BV139-S), in the second, already sensitized mice were treated (S-BV139). The results demonstrated that administering 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 group. Skin test reactivity to Bet v 1 was reduced in the BV139-S group. However, no differences in terms of specific antibody production between treated and untreated mice could be observed. This study provides evidence that administration of dominant T cell epitopes can down-regulate the allergen-specific T cell response. Proceeding on the assumption that the T lymphocyte response to allergens is crucial for the induction and maintenance of the allergic disease, a modulation of the immune response to allergens by treatment with T cell epitope peptides could represent a promising concept for immunotherapy in the future.
Bauer
L
L
Institute of General and Experimental Pathology, AKH, University of Vienna, Austria.
Bohle
B
B
Jahn-Schmid
B
B
Wiedermann
U
U
Daser
A
A
Renz
H
H
Kraft
D
D
Ebner
C
C
D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D052179:Antigens, Plant; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006967:Hypersensitivity / Q000276:immunology*; D016056:Immunodominant Epitopes / Q000008:administration & dosage / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology; D007279:Injections, Subcutaneous; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000276:immunology; D010940:Plant Proteins / Q000008:administration & dosage / Q000276:immunology*; D012882:Skin Tests; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000485:Allergens; D052179:Antigens, Plant; D016056:Immunodominant Epitopes; D010455:Peptides; D010940:Plant Proteins; C061312:Bet v 1 allergen, Betula