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Binding properties of monoclonal antibodies recognizing external epitopes of the human MDR1 P‐glycoprotein
Author(s) -
Schinkel Alfred H.,
Borst Piet,
Smit Jaap J. M.,
Wagenaar Els,
Dollé Martijn,
Arceci Robert J.,
Baas Frank,
Tsuruo Takashi,
Mechetner Eugene B.,
Roninson Igor B.
Publication year - 1993
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910550326
Subject(s) - monoclonal antibody , epitope , glycoprotein , p glycoprotein , microbiology and biotechnology , antibody , biology , extracellular , cell culture , transfection , biochemistry , multiple drug resistance , immunology , genetics , antibiotics
Monoclonal antibodies (MAbs) recognizing external epitopes of the human MDRI P‐glycoprotein have been used both for the detection of multidrug‐resistant cells and as specific inhibitors of P‐glycoprotein‐mediated multidrug resistance. Using a panel of recently developed transfected or transgenic cell lines containing variants of the human MDRI and MDR3 P‐glycoproteins, we have compared the specificity and binding properties of the previously isolated MAbs MRK16, HYB‐241, UIC2 and 4E3, and of the newly isolated MAb 7G4. The removal of 1, 2 or all 3 of the N‐glycosylation sites present in the first extracellular loop of MDR1 P‐glycoprotein did not significantly affect the binding of these MAbs. In contrast, a 20 amino acid deletion in the first extracellular loop of MDR1 P‐glycoprotein completely abolished binding of UIC2, whereas the binding of all other MAbs was hardly affected. None of the MAbs tested bound detectably to cell lines containing a high level of the human MDR3 P‐glycoprotein. The differences in the binding specificity between UIC2 and the other tested antibodies parallel the reported functional differences in the ability of these antibodies to inhibit P‐glycoprotein‐mediated drug efflux.