ISOLATION OF ANTIGENIC MIMICS OF MDR1-P-GLYCOPROTEIN BY PHAGE-DISPLAYED PEPTIDE LIBRARIES

To identify an MC57 epitope which is more efficiently expressed on ina ctivated forms of P-glycoprotein we utilized peptide libraries display ed on filamentous phage. Using this technology, we selected specific p hage clones blocking the binding of the murine monoclonal (MAb) MC57 w ith live human multi-drug-resistant (MDR) cells, and sequenced and ana lyzed their DNA. The results we obtained indicate that MAb MC57 epitop e could be formed by 2 regions localized on the predicted fourth and s ixth extracellular loops of the current 12-transmembrane-domain model predicted for MDRI-P-glycoprotein. Surprisingly, a third region, defin ed by residues 800-807 of the MDRI-P-glycoprotein sequence and postula ted to be intracellular, was also identified as a putative part of the MC57 epitope. This finding adds weight to the interesting hypothesis that a P-glycoprotein structure different from the current model may e xist. (C) 1995 Wiley-Liss, Inc.