Stimulation and inhibition of anti-hapten responses in guinea pigs immunized with hybrid liposomes.

Abstract

Guinea pigs were immunized with liposomal model membranes containing phosphatidylethanolamine (PE) or glycerophosphorylethanolamine (GPE) derivatives in which the amino function was substituted with dinitrophenylaminocaproyl (Dnp-Cap) or mono(p-azobenzenearsonic acid)tyrosyl (ABA-Tyr) residues. Previous studies demonstrated that hapten-specific antibodies are elicited by Dnp-Cap-PE or ABA-Tyr-PE sensitized liposomes and that cell-mediated immunity is induced by ABA-Tyr-PE (but not Dnp-Cap-PE) sensitized liposomes. These liposomes differ from conventional immunogens in which haptens are covalently attached to immunogenic carriers. This investigation describes 2 new aspects of liposomal immunogenicity in animals immunized with hybrid liposomes containing Dnp-Cap-PE and ABA-Tyr-PE: stimulation of the anti-Dnp response by incorporation of increasing amounts of ABA-Tyr-PE and inhibition of anti-ABA antibody formation by incorporation of increasing amounts of Dnp-Cap-PE. The 2 phenomena are dependent on the presence of each determinant in the same lipid bilayer. Entrapment of the water-soluble deacylated derivative of ABA-Tyr-PE (i.e., ABA-Tyr-GPE) in the aqueous compartments of Dnp-Cap-PE sensitized liposomes does not enhance anti-Dnp antibody production. Entrapment of the non-amphipathic derivative of Dnp-Cap-PE (i.e., Dnp-Cap-GPE) within ABA-Tyr-PE sensitized liposomes does not suppress anti-ABA anti-body formation. Mixtures of Dnp-Cap-PE sensitized liposomes and ABA-Tyr-PE sensitized liposomes neither stimulated nor inhibited the anti-hapten responses. Preparation of hybrid liposomes with different N-substituted PE derivatives may provide an extremely convenient method for controlling hapten and/or immunologic carrier determinant density.