PROSTATE-SPECIFIC ANTIGEN - CHARACTERIZATION OF EPITOPES BY SYNTHETICPEPTIDE-MAPPING AND INHIBITION STUDIES

To improve our understanding of the prostate-specific antigen (PSA) an tigenic regions, we studied the association targets of one anti-PSA po lyclonal antibody and 10 anti-PSA monoclonal antibodies (mAbs). We als o examined the ability of the mAbs to inhibit PSA enzymatic activity a nd block the association of PSA with a,antichymotrypsin (ACT). Linear epitope mapping with a polyclonal antibody indicated the presence of s ix major antigenic regions in PSA. Examination of the panel of mAbs es tablished that three of them bind to linear epitopes. Five of the mAbs inhibited >90% of PSA enzymatic activity. However, inhibition of PSA enzymatic activity and hindrance of PSA-ACT association by mAbs cannot be used to predict whether the mAbs bind to free PSA, the PSA-ACT com plex, or both. Some of the mAbs may block PSA-ACT association through peripheral occlusion of the binding site, or through induction of conf ormational changes in PSA.