SOLUBLE-PROTEINS MODIFIED WITH ACETALDEHYDE AND MALONDIALDEHYDE ARE IMMUNOGENIC IN THE ABSENCE OF ADJUVANT

Recent studies have shown that the alcohol metabolites malondialdehyde and acetaldehyde can combine to form a stable adduct (MAA) on protein s. This adduct has been detected in the livers of mts chronically cons uming ethanol, and serum antibodies to MAA have been observed at signi ficantly higher concentrations in ethanol-fed when compared with pair- fed or chow-fed control rats. More recently, preliminary studies have strongly suggested that the MAA adduct is capable of stimulating antib ody responses to soluble proteins in the absence of adjuvants. The ant ibodies produced recognize either the MAA epitope or the carrier prote in itself. Therefore, it was the purpose of this study to examine the potential immunogenicity of MAA-modified exogenous proteins in the abs ence of adjuvants. Balb/c mice were immunized in the presence or absen ce of adjuvant with different concentrations of unmodified or MAA-modi fied proteins. The antibody response to both the MAA epitope and unmod ified protein epitopes were determined by ELISA. In the absence of adj uvant, significant antibody responses were induced to both the MAA epi tope and nonmodified protein epitopes. Smaller immunizing doses of MAA -protein conjugate favored the production of antibodies to nonmodified proteins, whereas larger doses induced a strong anti-MAA response. In studies to begin determining a mechanism for the specificity of the r esponse in the absence of adjuvants, peritoneal macrophages were found to bind and degrade MAA-adducted proteins through the use of a scaven ger receptor. This indicated that MAA-adducted proteins may be specifi cally taken up and epitopes presented to the humoral immune system in the absence of adjuvants. Importantly, these are the first data showin g that an alcohol-related metabolite can induce an antibody response i n the absence of adjuvant and suggesting a mechanism by which antibody to the MAA adduct or its carrier (exogenous or endogenous) proteins m ay be generated in vivo.