The sequence A alpha-(148-160) in fibrin, but not in fibrinogen, is accessible to monoclonal antibodies.
Fibrin, but not fibrinogen, accelerates the activation of plasminogen catalyzed by tissue-type plaminogen activator. Previous work showed that essential information for this accelerating capacity of fibrin resides in the sequence corresponding to residues 148-160 of the A alpha chain of fibrinogen [A alpha-(148-160)]. Our working hypothesis, based on those findings, is that A alpha-(148-160) is buried in fibrinogen and becomes accessible to proteins such as plasminogen and/or tissue-type plasminogen activator when fibrinogen is converted to fibrin. To test this hypothesis we have raised a monoclonal antibody against synthetic A alpha-(148-160) and found that this antibody reacts with fibrin and not with fibrinogen. This finding shows that A alpha-(148-160) becomes accessible when fibrinogen is converted to fibrin and that A alpha-(148-160) is a fibrin-specific neoantigenic determinant.
Schielen
W J
WJ
Gaubius Institute, Nederlandse Organisatiè voor Toegepast Natuurwetenschappelÿk Onderzoek, Leiden, The Netherlands.
Voskuilen
M
M
Tesser
G I
GI
Nieuwenhuizen
W
W
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification; D000936:Antigen-Antibody Complex; D005260:Female; D005337:Fibrin / Q000276:immunology*; D005340:Fibrinogen / Q000276:immunology*; D006801:Humans; D007202:Indicators and Reagents; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology; D013329:Structure-Activity Relationship
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D007202:Indicators and Reagents; D009842:Oligopeptides; D005337:Fibrin; D005340:Fibrinogen