Expression of a Human IgG4 Antibody, BAB2, with Specificity for the Major Birch Pollen Allergen, Bet v 1 in Escherichia coli: Recombinant BAB2 Fabs Enhance the Allergic Reaction

Abstract

Background: Antigen recognition by antibodies of different isotypes can result in completely different effects as exemplified by Type I allergy. While the IgE–antibody–mediated release of biological mediators constitutes the immunopathological basis for the immediate symptoms observed in allergic patients, allergen–specific IgG antibodies are thought to have protective effects. Methods: Cell lines secreting five human monoclonal IgG antibodies (BAB1–BAB5) with specificity for the major birch pollen allergen Bet v 1 were established from a birch–pollen–allergic patient who had received birch– pollen–specific immunotherapy. The influence of the Bet v 1–specific IgG antibodies on IgE binding to Bet v 1 was investigated. BAB2 was expressed in Escherichia coli as recombinant Fab, purified and tested for its ability to modulate Bet v 1–induced immediate–type skin reactions. Results: The BAB antibodies belonged to different IgG subclasses (BAB1: IgG1; BAB2, BAB3, BAB5: IgG4; and BAB4: IgG2) reflecting a tendency towards Th2. BAB1 represented the only antibody which strongly blocked IgE binding to Bet v 1, whereas BAB 3–BAB5 had little effect on IgE binding. Surprisingly, natural BAB2 antibodies as well as recombinant BAB2 Fabs strongly enhanced IgE binding to Bet v 1 and Bet v 1–induced immediate–type skin reactions and thus represent ‘enhancing antibodies’. Conclusion: The demonstration that anti–allergen IgG antibodies can also enhance IgE binding to a given allergen explains the unpredictability of specific immunotherapy as well as the controversy on the role of IgG in atopy.

Epitope Mapping of Lysozyme Using the Chinese Egg-Allergic Sera at Both Pooled and Individual Levels

“…Meanwhile, IgG is critical to the success of allergen-specific immunotherapy . IgG-binding epitopes can affect the binding of IgE to its antigenic epitope . Therefore, the binding of B-cell linear epitopes of LYS to IgG should be equally concerned about.…”

“…41 IgG-binding epitopes can affect the binding of IgE to its antigenic epitope. 42 Therefore, the binding of B-cell linear epitopes of LYS to IgG should be equally concerned about. Among the seven IgE-binding linear epitopes mapped by the dot-blot assay, AA18−22, AA63−73, AA75−79, and AA115−117 were highly coincident with the predicted results.…”

Antibodies and superantibodies in patients with chronic rhinosinusitis with nasal polyps

“…However, there is a precedent in the case of the antibody BAB2 against a dominant birch pollen allergen, Bet v 1 58 . BAB2 and, notably, its Fab enhanced binding of Bet v 1 to IgE and caused immediate-type hypersensitivity reactions in human skin.…”

“…BAB2 and, notably, its Fab enhanced binding of Bet v 1 to IgE and caused immediate-type hypersensitivity reactions in human skin. The authors suggested that enhancing antibodies could account for the failure of specific allergen immunotherapy 58, 59, 60. Although enhancing antibodies are relatively rare, they might be important because their activity might “win” in competition with an excess of blocking antibodies.…”