THE ONCOFETAL J28 EPITOPE INVOLVES FUCOSYLATED O-LINKED OLIGOSACCHARIDE STRUCTURES OF THE FETOACINAR PANCREATIC PROTEIN

The fetoacinar pancreatic protein (FAP), characterized by the mAb J28, is an oncofetal form of bile salt dependent lipase (BSDL), the expres sion of which is related to pancreatic differentiation and neoplastic processes, Because the J28 epitope, recognized by mAb J28, is suggeste d to be dependent upon carbohydrates, we have attempted to gain inform ation about the structure of this epitope, Indeed, treatment of FAP wi th sodium periodate abolished the reactivity of the protein to mAb J28 , which demonstrates the implication of oligosaccharides in the struct ure of the J28 epitope, FAP offers both O-linked and N-linked carbohyd rate structures, of which, as we have determined, one is involved, Pep tides obtained after cyanogen bromide cleavage were desialylated then separated by affinity chromatography on an immobilized peanut agglutin in agarose column, The peptide retained on this column carried out the reactivity with the mAb J28, Although some differences in amino acid analysis were observed, the N-terminal sequence of this peptide correl ates with that of the C-terminal part of the enzyme, Carbohydrate anal ysis of the peptide bearing the J28 epitope revealed fucose, galactose , N-acetylgalactosamine, N-acetylglucosamine, and N-acetylneuraminic a cid, The competition observed between mAb J28 and Ulex europaeus I lec tin for binding to the J28 epitope suggested that fucose residue a (1- 2) linked to a galactose residue was implicated in the structure of th e J28 epitope, Alternatively, the loss of the mAb J28 reactivity upon treatment of FAP either with bovine kidney or bovine epididymis fucosi dase was observed indicating that fucose residues linked at the a (1-2 ) and a (1-6) positions may be involved in the establishment of the st ructure of the J28 epitope, These observations suggest that mAb J28 re cognized a particular fucosylated O-linked oligosaccharide structure l ocated at the mucin-like extended C-terminal part of FAP.