Structure of a patient-derived antibody in complex with allergen reveals simultaneous conventional and superantigen-like recognition

Significance We have discovered that a human antibody can simultaneously bind two molecules of antigen, in this case a grass pollen allergen, one in a conventional manner and the other unconventionally. The two allergen molecules also bridge two identical antibodies. These observations challenge the dogma that one antibody recognizes only a single antigen/allergen epitope. The mechanism of antibody cross-linking seen here may explain the potency of certain allergens in triggering an allergic reaction, extending our understanding of the nature of allergenicity and informing the design of hypoallergenic molecules for allergen immunotherapy. This dual reactivity and potential for cross-linking surface immunoglobulin on B cells suggests mechanisms by which human autoimmune and other diseases might be initiated.