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Characterization of common neoantigenic epitopes generated in plasminogen activator inhibitor‐1 after cleavage of the reactive center loop or after complex formation with various serine proteinases
Author(s) -
Debrock Sophie,
Declerck Paul J.
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)01289-0
Subject(s) - epitope , plasmin , monoclonal antibody , microbiology and biotechnology , plasminogen activator , serine , chemistry , thrombin , plasminogen activator inhibitor 1 , biochemistry , cleavage (geology) , antibody , biology , enzyme , immunology , platelet , genetics , paleontology , fracture (geology)
Plasminogen activator inhibitor‐1 (PAI‐1), an important risk factor for thrombotic diseases, is a member of the superfamily of serine proteinase inhibitors. To define structural rearrangements occurring during interaction between PAI‐1 and its target proteinases we have raised monoclonal antibodies against the PAI‐1/t‐PA complex. Thirteen out of 401 monoclonal antibodies reacted preferentially with the PAI‐1/t‐PA complex as compared to free PAI‐1 or free t‐PA. Detailed characterization revealed the presence of two non‐overlapping neoantigenic epitopes in the PAI‐1/t‐PA complex. Both neoantigenic epitopes were also exposed after complex formation between PAI‐1 and either urokinase‐type plasminogen activator, plasmin or thrombin as well as after cleavage of the reactive site loop of non‐inhibitory substrate type PAI‐1 variants. Thus, we have identified two neoantigenic epitopes, localized entirely in PAI‐1, and commonly exposed after complex formation of active PAI‐1 with various proteinases or after cleavage of substrate PAI‐1. These monoclonal antibodies should facilitate further studies on the mechanism of interaction between various PAI‐1 forms and its target proteinases.