The N-domain of the biliary glycoprotein (BGP) adhesion molecule mediates homotypic binding: domain interactions and epitope analysis of BGPc.

The biliary glycoproteins (BGPs) represent a group of at least eight differentially spliced molecules belonging to the carcinoembryonic antigen (CEA) subgroup of the CEA family. These molecules are recognized by the CD66 monoclonal antibodies (MoAbs) and function as homotypic and heterotypic adhesion molecules. The extracellular region of the BGPc splice variant comprises an N-terminal IgV-like domain and three IgC2-set domains (A1, B1, and A2). Using soluble recombinant BGP domain variants, we demonstrate in this report that the N-terminal domain mediates homotypic adhesion. Furthermore, this adhesion is both temperature- and cation-dependent. The soluble domain variants of BGP are ideal molecules for epitope mapping. Using these constructs, we have mapped 11 MoAbs that react with the CEA family to different domains of BGPc and have shown that the CD66 MoAbs, YTH71.3.2 and CLBgran 10 (M38), recognize epitopes in the N-terminal domain.