title: P-glycoprotein epitope mapping. II. The murine monoclonal antibody MM6.15 to human multidrug-resistant cells binds with three distinct loops in the MDR1-P-glycoprotein extracellular domain.
abstract: A new murine monoclonal antibody (MAb), MM6.15, to human MDR1 P-glycoprotein was found to be reactive in ELISA with synthetic peptides selected from the predicted sequences of the first, fourth and sixth extracellular loop of MDR1-P-glycoprotein. In order to precisely define the MM6.15-binding site, a peptide library of overlapping 5- to 9-mer residues covering the entire sixth extracellular loop of both human and rodent class-1 P-glycoproteins was synthesized on polyethylene pins and tested for MAb binding. The results of this ELISA demonstrated that the MAb MM6.15 reacts only with human synthetic peptides and that the critical component of the MAb recognition is made up of the amino-acid sequence LVAHKL (residues 963-968 of the MDR1-P-glycoprotein) with histidine (H), lysine (K) and possibly leucine (L), key residues of this immunogenic domain.
authors.affiliation: Laboratorio di Immunologia, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Cianfriglia
authors.forename: G
authors.initials: G
authors.lastname: Romagnoli
authors.forename: M
authors.initials: M
authors.lastname: Tombesi
authors.forename: F
authors.initials: F
authors.lastname: Poloni
authors.forename: G
authors.initials: G
authors.lastname: Falasca
authors.forename: F
authors.initials: F
authors.lastname: Di Modugno
authors.forename: M
authors.initials: M
authors.lastname: Castagna
authors.forename: A
authors.initials: A
authors.lastname: Chersi
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis / Q000276:immunology* / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism*; D000918:Antibody Specificity; D001665:Binding Sites; D006224:Cricetinae; D018432:Drug Resistance, Multiple / Q000235:genetics / Q000502:physiology*; D018604:Epitope Mapping; D005110:Extracellular Space / Q000378:metabolism; D006639:Histidine / Q000378:metabolism; D006801:Humans; D007930:Leucine / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D006639:Histidine; D007930:Leucine; D008239:Lysine