Analysis of the specificity of CEA reactive monoclonal antibodies. Immunological support for the domain-model of CEA

A panel of 17 monoclonal antibodies (MAbs), which are reactive with purified carcinoembryonic antigen (CEA), was tested. The MAbs were categorized into 6 groups according to their reactivity with CEA 180, CEA 160, non-specific cross-reacting antigen (NCA) 97 and NCA 50. After chemical modification of CEA (reduction, carboxymethylation, deglycosylation, enzymatic cleavage) and binding studies, the MAbs were further divided into 8 subgroups, representing 8 different antigenic sites on CEA. All MAbs bind to deglycosylated CEA. Most of the MAbs are directed against conformational determinants, since only three of them recognize reduced and alkylated CEA. The same three MAbs are able to detect 29 kDa glycosylated fragments obtained by enzymatic cleavage of CEA. These three protease V8- and trypsin-resistant fragments, probably obtained by interdomain cleavage, show a close relationship in peptide patterns, supporting the repeating structural domain-model of CEA as deduced from the cDNA sequence of CEA.