Selective inhibition of integrin function by antibodies specific for ligand-occupied receptor conformers

We have hypothesized that ligand-induced binding sites (LIBS), i.e. sites expressed on cell surface receptors only after ligand binding causes the receptor to change shape, mediate subsequent biological events. To test this hypothesis, we have raised monoclonal antibodies that preferentially react w...

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Bibliographic Details
Published in:The Journal of biological chemistry 1990-04, Vol.265 (11), p.6346-6352
Main Authors: A L Frelinger, 3rd, I Cohen, E F Plow, M A Smith, J Roberts, S C Lam, M H Ginsberg
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Antibodies, Monoclonal - isolation & purification
Antibody Specificity
Antigen-Antibody Complex
Biological and medical sciences
Blood Coagulation Tests
Blood Platelets - cytology
Blood Platelets - physiology
Cell receptors
Cell structures and functions
Chromatography, Affinity
Enzyme-Linked Immunosorbent Assay
Fundamental and applied biological sciences. Psychology
Humans
Integrins - immunology
Integrins - physiology
Kinetics
Ligands
Miscellaneous
Molecular and cellular biology
Molecular Sequence Data
Oligopeptides - chemical synthesis
Platelet Membrane Glycoproteins - immunology
Platelet Membrane Glycoproteins - isolation & purification
Platelet Membrane Glycoproteins - physiology
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Summary:We have hypothesized that ligand-induced binding sites (LIBS), i.e. sites expressed on cell surface receptors only after ligand binding causes the receptor to change shape, mediate subsequent biological events. To test this hypothesis, we have raised monoclonal antibodies that preferentially react with an integrin (platelet glycoprotein (GP) IIb-IIIa) after it bind Arg-Gly-Asp-containing ligands. The 13 anti-LIBS antibodies obtained define at least three distinct GPIIb-IIIa epitopes; one of these epitopes is also expressed following occupancy of another integrin, the vitronectin receptor. Certain of these LIBSs appear to mediate functions, since the antibodies that define them inhibit GPIIb-IIIa-mediated fibrin clot contraction or platelet adhesion to collagen. Nevertheless, none of the anti-LIBS antibodies inhibit binding of the primary ligand, fibrinogen. These data indicate that LIBS may mediate distinct consequences of receptor occupancy.
ISSN:0021-9258
1083-351X
DOI:10.1016/s0021-9258(19)39332-9