Modulation of the Immune Response to Allergens: Phospholipase A Degradation Products Suppress IgG and IgE Response in Mice

Abstract

Degradation products of phospholipase A2 (PLA2), the major allergen of honeybee venom, were prepared by peptic digestion of the enzyme and fractionated by molecular exclusion chromatography. The largest of the isolated products, P-1, was found to be a centrally nicked PLA2 molecule with a loss of several amino acids. It was examined for its antigenic, immunogenic and immunosuppressive properties. This peptic product was unable to block antigen-antibody reactions between PLA2 and anti-PLA2 antibodies and was incapable of inducing passive cutaneous anaphylaxis in rat skin sensitized with mouse anti-PLA2 IgE antibodies. BDF1 female mice injected intravenously with P-1 exhibited suppressed IgG and IgE anti-PLA2 responses to a subsequent PLA2 immunization. Intravenous administration of P-1 to mice with ongoing immune response to PLA2 resulted in decline of antigen-specific IgE titers. Transfer of splenic T cells from mice injected with P-1 into naive recipients caused profound suppression of the response to subsequent immunization with PLA2 indicating presence of PLA2-specific T suppressor cells. These results indicate that a degradation product of PLA2 prepared by peptic digestion lost antigenic and immunogenic properties of the intact enzyme but retained immunosuppressive properties, thus offering a novel approach to allergen immunotherapy.