Immunological Heterogeneity of Carcinoembryonic Antigen: Antigenic Determinants on Carcinoembryonic Antigen Distinguished by Monoclonal Antibodies1

Murine monoclonal ant ibodies against carc inoembryonic antigen (CEA) derived from a colonic tumor were analyzed by radioimmunoassay for reactivity with CEA and the CEA-related antigens, meconium antigen (MA) and nonspecif ic cross-reacting antigen. Ant ibody-ant igen binding profiles revealed three classes of hybridomas. The Class I antibody, NP-1, recognized an epitope shared among all three antigens, and its affinity for CEA and MA was high but low for nonspecif ic cross-react ing antigen. The Class II ant ibodies reacted with sites shared between CEA and MA, while those of the Class III type only bound CEA. The Class III antibody, NP-4, bound less than 50% of the CEA molecules recognized by goat specif ic anti-CEA ant ibody and the other classes of monoclonal antibodies. Two Class II antibodies, NP-2 and NP-3, bound similar amounts of CEA and MA with moderate but different affinities for CEA. Studies using labeled monoclonal ant ibodies for CEA epitope blocking revealed that NP-2 and NP-3 recognize two separate epitopes on CEA within the Class II category. Thus, monoclonal antibodies to CEA can dif ferentiate at least four antigenic sites on colonic cancer CEA. One is shared by CEA, MA, and nonspecif ic cross-react ing antigen; two others are shared by CEA with MA; and a fourth appears specif ic for a subpopulat ion of CEA molecules.