title: Isolation of antigenic mimics of MDR1-P-glycoprotein by phage-displayed peptide libraries.
abstract: To identify an MC57 epitope which is more efficiently expressed on inactivated forms of P-glycoprotein we utilized peptide libraries displayed on filamentous phage. Using this technology, we selected specific phage clones blocking the binding of the murine monoclonal (MAb) MC57 with live human multi-drug-resistant (MDR) cells, and sequenced and analyzed their DNA. The results we obtained indicate that MAb MC57 epitope could be formed by 2 regions localized on the predicted fourth and sixth extracellular loops of the current 12-transmembrane-domain model predicted for MDR1-P-glycoprotein. Surprisingly, a third region, defined by residues 800-807 of the MDR1-P-glycoprotein sequence and postulated 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 exist.
authors.affiliation: Laboratorio di Immunologia, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Poloni
authors.forename: G
authors.initials: G
authors.lastname: Romagnoli
authors.forename: M
authors.initials: M
authors.lastname: Cianfriglia
authors.forename: F
authors.initials: F
authors.lastname: Felici
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000276:immunology*; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D018604:Epitope Mapping; D015723:Gene Library; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000032:analysis
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D010455:Peptides