title: Accessibility of epitopes on fibrin clots and fibrinogen gels.
abstract: Radiolabeled antibodies were perfused into fibrin clots and fibrinogen gels formed in vitro to assess the reactivity of selected epitopes. An antifibrinogen monoclonal antibody (MoAb) (antibody 1D4/xl-f), directed against an epitope in the A alpha-chain C-terminal region (A alpha 241-476), bound to 35% of the epitope in crosslinked fibrin clots and 37% of the same epitope in factor XIII-induced fibrinogen gel networks. A different MoAb (4-2/xl-f, anti gamma 392-406) bound to only 7% of the epitope in both fibrin and fibrinogen gels. As expected, an antifibrin MoAb (antibody T2G1, antiB beta 15-21) did not bind to fibrinogen gels, but bound to fibrin, although to only 14% of the available T2G1-reactive epitopes. An antibody that does not recognize fibrin (antibody 1-8C6, antiB beta 1-21) predictably did not bind to fibrin clots and bound to 35% of the 1-8C6 epitopes present in fibrinogen gels, a level of binding also observed with antibody T2G1 and fibrinogen gels only after the latter were treated with thrombin. T2G1 epitope expression was affected much more than 1D4/xl-f epitope expression in clots formed in buffers of high or low ionic strength, conditions known to influence clot structure. Studies on the availability, in quantitative terms, of the T2G1-reactive epitope in fibrin clots is of particular importance because this antibody is currently being used in clinical trials as a clot imaging agent.
authors.affiliation: Department of Blood Coagulation Biochemistry, New York Blood Center, NY 10021.
authors.forename: R
authors.initials: R
authors.lastname: Procyk
authors.forename: B
authors.initials: B
authors.lastname: Kudryk
authors.forename: S
authors.initials: S
authors.lastname: Callender
authors.forename: B
authors.initials: B
authors.lastname: Blombäck
mesh_terms: D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D001777:Blood Coagulation; D000939:Epitopes / Q000032:analysis*; D005337:Fibrin / Q000276:immunology / Q000502:physiology*; D005340:Fibrinogen / Q000276:immunology / Q000502:physiology*; D005782:Gels; D006801:Humans; D007700:Kinetics; D008024:Ligands
chemical_list: D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000939:Epitopes; D005782:Gels; D008024:Ligands; D005337:Fibrin; D005340:Fibrinogen