The sequence Aα-(148-160) in fibrin, but not in fibrinogen, is accessible to monoclonal antibodies

Abstract

Fibrin, but not fibrinogen, accelerates the activation of plasminogen catalyzed by tissue-type plasminogen activator. Previous work showed that essential information for this accelerating capacity of fibrin resides in the sequence corresponding to residues 148-160 of the Aα chain of fibrinogen [Aα-(148-160)]. Our working hypothesis, based on those findings, is that Aα-(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 Aα-(148-160) and found that this antibody reacts with fibrin and not with fibrinogen. This finding shows that Aα-(148-160) becomes accessible when fibrinogen is converted to fibrin and that Aα-(148-160) is a fibrin-specific neoantigenic determinant.