Induction of IgE antibodies' in mice and rhesus monkeys with recombinant birch pollen allergens: Different allergenicity of Bet v 1 and Bet v 2

Background: Serologic measurements with recombinant birch pollen allergens, rBet nu 1 and rBet nu 2 (birch profilin), have shown that more than 95% of patients allergic to tree pollen mount high levels of IgE against rBet nu 1, whereas only approximately 10% of the patients display rather low levels of IgE against rBet nu 2. Objective: In this study an attempt was made to determine whether the different allergenicity of the major birch pollen allergen, rBet nu 1, and a minor birch pollen allergen, rBet nu 2, might be related to a different immunogenicity of the proteins as evaluated in experimental animal systems (mice and rhesus monkeys). Methods: Purified recombinant allergens were injected into mice and rhesus monkeys with aluminum hydroxide as adjuvant for elicitation of specific IgE responses. Antibody responses to the allergens were detected by immunoblotting, and time courses of immune responses were measured by ELISA. Results: In both animal models more than the 10-fold dose of rBet nu 2 was required to induce IgE antibodies, and even then, the amount of specific IgE antibodies elicited with rBet nu 1 was substantially higher than that induced by rBet nu 2. It was noted that rBet nu 2 formed stable polymers through disulfide bonds. Conclusion: In two different animal models (mice and rhesus monkeys) the major birch pollen allergen rBet nu 1, induced substantially higher levels of IgE than rBet nu 2. A reduced allergenicity of Bet nu 2 caused by polymer formation would be in agreement with previous studies indicating reduced allergenicity of proteins on chemical polymerization.