Mapping epitope characteristics on carcinoembryonic antigen.

A method of epitope analysis is described in which the binding of one monoclonal antibody (MAb) to radiolabeled carcinoembryonic antigen (CEA) competes with the subsequent binding of an immobilised second MAb. From the degree of blocking obtained, we have identified both structurally related and independent epitopes on CEA. Using this technique to study fifteen MAbs, we have been able to recognise at least 6 unrelated epitopes of the CEA glycoprotein. Further characterisation of these epitopes was accomplished by means of immunohistochemistry. Of the fifteen MAbs, 6 were specific for CEA and reacted with at least 3 unrelated regions of the glycoprotein. Of the remaining 9 MAbs, 2 cross-reacted with erythrocytes, 5 with components of liver and 7 with polymorphonuclear neutrophils. Cross-reactions with liver were varied showing differential antibody specificity for bile canaliculi, Kupffer cells and bile duct epithelium. A high degree of correlation between epitope relatedness and immunohistochemical specificity was found. Two CEA-specific and 4 cross-reactive MAbs were also shown to react with ion-sensitive sites on the CEA glycoprotein.