Immunological heterogeneity of carcinoembryonic antigen: antigenic determinants on carcinoembryonic antigen distinguished by monoclonal antibodies.

Murine monoclonal antibodies against carcinoembryonic antigen (CEA) derived from a colonic tumor were analyzed by radioimmunoassay for reactivity with CEA and the CEA-related antigens, meconium antigen (MA) and nonspecific cross-reacting antigen. Antibody-antigen 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 nonspecific cross-reacting antigen. The Class II antibodies 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 specific anti-CEA antibody 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 antibodies 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 differentiate at least four antigenic sites on colonic cancer CEA. One is shared by CEA, MA, and nonspecific cross-reacting antigen; two others are shared by CEA with MA; and a fourth appears specific for a subpopulation of CEA molecules.