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Interaction of Antigens with Dimethyldioctadecylammonium Bromide, a Chemically Defined Biological Response Modifier¹

Department of Surgery [F. S. B., M. D. P.] and Biochemistry [M. D. P.], University of Texas Health Science Center, Dallas Texas 75235

Dimethyldioctadecylammonium bromide (DDA) stimulates immune responses, primes (or activates) macrophages, and binds to antigens. Because relatively little is known about the binding of adjuvants to antigens, the nature of the interaction of DDA with soluble protein and cellular antigens was investigated. Dose-dependent, stable complexes are formed between cells and the lipoidal cation of DDA. Since the interaction is independent of negatively charged sialic acid residues of the cell membrane and little DDA binds to intracellular structures, it is suggested that binding occurs primarily at the cell membrane, probably through hydrophobic interaction with lipids. The idea of membrane perturbation is supported by the leak of macromolecules (lactic dehydrogenase) from treated cells. Reaction of varying amounts of DDA with a constant amount of ovalbumin was also dose dependent. Because of a minimal effect of ionic strength on the reaction, it is concluded that ionic interaction may make a minor contribution to product formation. Complexes of DDA and antigen are particularly effective in eliciting a delayed hypersensitivity reaction, which has been postulated to be desirable for an antitumor effect.

¹ This study was supported by a grant from the Carl B. and Florence E. King Foundation.

² To whom requests for reprints should be addressed.

Received 6/17/82. Accepted 8/26/82.