SUCCESSFUL IMMUNOTHERAPY WITH T-CELL EPITOPE PEPTIDES OF BEE VENOM PHOSPHOLIPASE-A2 INDUCES SPECIFIC T-CELL ANERGY IN PATIENTS ALLERGIC TO BEE VENOM

Background: Specific immunotherapy with honeybee venom (BV) is highly effective, but allergic side effects can occur during treatment. Immun otherapy with peptides containing major T-cell epitopes of the relevan t allergen or allergens pro,ides an alternative strategy without these problems. Objective: The study investigates the immunologic mechanism s and clinical effects of immunotherapy with T-cell epitope peptides o f the major BV allergen, the phospholipase A2 (PW). Methods: Five pati ents with IgE-mediated systemic allergic reactions to bee stings were treated with a mixture of three T-cell epitope peptides of PLA. Ten pa tients allergic to BV receiving whole BV immunotherapy served as contr ol subjects. Increasing doses of the peptide mixture, up to a maintena nce dose of 100 mu g, were administered subcutaneously within 2 months . The patients were then challenged with PLA and 1 week later with a b ee sting. The cellular and humoral immune response was measured in vit ro. Results: No allergic side effects were caused by the peptide immun otherapy, and all patients tolerated the challenge with PLA without sy stemic allergic symptoms. Two patients developed mild systemic allergi c reactions after the bee sting challenge. After peptide immunotherapy , specific proliferative responses to PLA and the peptides in peripher al blood mononuclear cells were decreased in successfully treated pati ents. The production of T-H2 and T-H1 cytokines was inhibited, and B c ells were not affected in their capacity to produce specific IgE and I gG4 antibodies. Their levels increased after allergen challenge in fav or of IgG4. Conclusions: Immunotherapy of BV allergy with short T-cell peptides of PLA induces epitope-specific anergy in peripheral T cells and changes the specific isotype ratio in a fashion similar to that o f conventional immunotherapy in successfully treated patients.