HUMAN-ANTIBODIES AGAINST THE POLYMORPHIC EPITHELIAL MUCIN IN OVARIAN-CANCER PATIENTS RECOGNIZE A NOVEL SEQUENCE IN THE TANDEM REPEAT REGION

The humoral immune response to the polymorphic epithelial mucin (PEM) was studied by characterising the reactivity of human antibodies gener ated by EBV-immortalised B-cells from tumour-draining lymph nodes of o varian cancer patients. All the human antibodies, selected in ELISA fo r their reactivity to the protein core tandem repeat sequence, reacted with PEM-expressing tumour cells. Aberrant glycosylation of the pepti de core of the PEM molecule in cancer cells leads to the exposure of p eptide epitopes that can be considered tumour specific. The epitope ma pping of six human antibodies revealed that only one of them contained the PDTR sequence, shown to be the immunodominant epitope in the mous e. Four of the six human antibodies recognised a novel common immunoge nic sequence (APPAH) in the tandem repeats. The binding of these human antibodies did not appear to be modulated by the length of the carboh ydrate side chains, as shown by O-glycosylation inhibition studies. Th ese results indicate that distinct sequences within the tandem repeat of PEM are target for a humoral immune response in humans. The presenc e of antibodies directed against different epitopes within the same an tigenic region may modulate the antigen presentation process and the o ngoing immune response. These data may help in clarifying the mechanis ms of the immune response to PEM in cancer patients for the developmen t of PPM-based immunotherapy. Copyright (C) 1996 Published by Elsevier Science Ltd