The antigenic surface of human chorionic gonadotropin as mapped by murine monoclonal antibodies.

We present a map describing the antigenic determinants (epitopes) of the human CG (hCG) molecule. A panel of monoclonal antibodies to hCG, previously characterized by us was incorporated into two-site binding assays to probe hCG by a 21 X 11 matrix of 231 pairs of MCA. Nine different reaction patterns of reciprocal homology were distinguished and interpreted as representing nine separate and distinct epitopes. Three of them localize on the alpha-subunit, 4 on the beta-subunit and 2 were expressed by the intact hCG (holo-hCG) molecule only, hence designated conformational (c) epitopes. Epitope-contingency analysis revealed that each of the 2 subunits of hCG possesses 1 epitope that is neither adjacent to nor overlapping with any of the other 8 epitopes. The latter were arranged in a complex cluster from which the c-epitopes protrude. Whereas the alpha- and c-epitopes are specific for glycoprotein hormones of human origin and for hCG, respectively, the beta-epitopes appeared to be evolutionarily highly conserved structures: with 1 exception, they were also present on the beta-chain of LH from many different mammalian species.