A cleavage-associated neoantigenic marker for a gamma chain site in the NH2-terminal aspect of the fibrinogen molecule

• Published in: The Journal of biological chemistry 1975-05, Vol.250 (9), p.3386-3392
• Main Authors: Plow, E F, Edgington, T S
• Format: Article
• Language: English
• Subjects: Animals; Antigen-Antibody Reactions; Binding Sites, Antibody; Chymotrypsin; Epitopes; Fibrinogen - immunology; Fibrinolysin; Guanidines; Hot Temperature; Humans; Molecular Weight; Peptide Fragments - isolation & purification; Protein Denaturation; Rabbits - immunology; Trypsin
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(19)41527-5

The E fragment, derived from the NH2-terminal aspect of fibrinogen by plasmin cleavage (fg-E), possesses two generically distinct sets of antigenic expressions. The major set of antigens is expressed by the parent molecule as indicated by the capacity of a major subpopulation of antibodies present in antiserum to fg-E and reactive with fg-E to: (a) react with fibrinogen, and (b) be specifically absorbed by fibrinogen but appears following proteolysis with plasmin. These cleavage associated neoantigens (fg-E-neo) specifically react with a minor subpopulation of antibodies present in antiserum to fg-E.E fragments isolated after varying exposures to plasmin all expressed fg-E-neo, but early E fragments exhibited quantitatively less neoantigenic expression than more extensively degraded E fragments. The entire fg-E-neo expression is recovered on a single isolated constituent chain of the E fragment, and immunochemical analysis with antiserum to the isolated constituent chain-bearing fg-E-neo identifies it as a derivative of the gamma chain constituent, exhibits marked stability to physicochemical denaturation and enzymatic degradation. These properties suggest that the neoantigen may be associated with a specific amino acid sequence which is exposed by the cleavage process. The identification and localization of fg-E-neo provides a specific molecular marker site for the characterization of structural and conformational changes associated with catabolism and function of fibrinogen.