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. 1972 Jan;69(1):208–212. doi: 10.1073/pnas.69.1.208

Molecular Events Responsible for Modulation of Neoantigenic Expression: The Cleavage-Associated Neoantigen of Fibrinogen

Edward Plow 1, Thomas S Edgington 1
PMCID: PMC427577  PMID: 4109598

Abstract

Molecular events responsible for modulation of neoantigenic expressions of a defined molecule have been explored in relation to three hypothetical molecular models (see below). Fibrinogen and its cleavage-associated neoantigen have been used as a prototype system. Physicochemical and enzymatic factors influencing neoantigenic expression were evaluated. The cleavage-associated neoantigen was not only exposed by plasmin and enzymes of similar specificity, but also in a qualitatively and quantitatively deficient fashion by enzymes of differing specificities. Denaturation of fibrinogen via reduction or pH alteration did not induce the neoantigen, but oxidation of the native fibrinogen molecule did elicit this neoantigenic expression. The neoantigen, once exposed on the D-fragment, was relatively stable to physical and chemical denaturation. These results are inconsistent with proposed cleavage site specific and neoconformational determinant models and are consistent with a steric model, which postulates that the cleavage-associated neoantigenic determinant is buried in native fibrinogen but is exposed in certain altered molecular species. The importance of molecular conformation in the exposure of antigenic expressions of a molecule and in modulation of the binding affinity of a neoantigen for specific antibody is demonstrated.

Keywords: blood coagulation, fibrinogen cleavage products, fibrinolysis, molecular conformation

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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