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 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.
Frelinger
A L
AL
Committee on Vascular Biology, Research Institute of Scripps Clinic, La Jolla, California 92037.
Cohen
I
I
Plow
E F
EF
Smith
M A
MA
Roberts
J
J
Lam
S C
SC
Ginsberg
M H
MH
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000302:isolation & purification; D000918:Antibody Specificity; D000936:Antigen-Antibody Complex; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000166:cytology / Q000502:physiology; D002846:Chromatography, Affinity; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016023:Integrins / Q000276:immunology / Q000502:physiology*; D007700:Kinetics; D008024:Ligands; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis; D010980:Platelet Membrane Glycoproteins / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D016023:Integrins; D008024:Ligands; D009842:Oligopeptides; D010980:Platelet Membrane Glycoproteins