Preferential recognition of the very low-density lipoprotein receptor ligand binding site by antibodies from phage display libraries.
Screening of a phage library displaying single chain fragments of the variable regions of human immunoglobulins (scFv) for binding to the ovarian chicken very low-density lipoprotein/vitellogenin receptor (OVR) led to the isolation of several antibody fragments with high affinity. As for the natural ligands of OVR, receptor binding of all antibody fragments is strictly Ca(2+)-dependent and is prevented by receptor-associated protein (RAP). Moreover, attachment of human rhinovirus serotype 2 (HRV2) to this receptor is inhibited by all scFvs. In contrast to conventional immunization, the in vitro selection method thus exclusively led to antibodies that attach to or close to the ligand binding site and thereby block the receptor-ligand interaction.
Institute of Biochemistry, Medical Faculty, University of Vienna, Austria.
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Pfistermueller
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Blaas
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Hodits
D000595:Amino Acid Sequence; D000818:Animals; D001435:Bacteriophages / Q000235:genetics / Q000276:immunology*; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism; D003001:Cloning, Molecular / Q000379:methods; D004527:Egg Proteins; D000939:Epitopes / Q000378:metabolism; D015723:Gene Library; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007106:Immune Sera; D007135:Immunoglobulin Variable Region / Q000378:metabolism*; D026563:LDL-Receptor Related Protein-Associated Protein; D008969:Molecular Sequence Data; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000378:metabolism*; D011973:Receptors, LDL / Q000276:immunology / Q000378:metabolism*; D012229:Rhinovirus / Q000276:immunology
D002352:Carrier Proteins; D004527:Egg Proteins; D000939:Epitopes; D006023:Glycoproteins; D007106:Immune Sera; D007135:Immunoglobulin Variable Region; D026563:LDL-Receptor Related Protein-Associated Protein; D011956:Receptors, Cell Surface; D011973:Receptors, LDL; C036053:VLDL receptor; C030474:vitellogenin receptor; D002118:Calcium