Immunobiology of Fibrinogen. EMERGENCE OF NEOANTIGENIC EXPRESSIONS DURING PHYSIOLOGIC CLEAVAGE IN VITRO AND IN VIVO

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Abstract

Physiological degradation of fibrinogen by plasmin leads to a recognized series of intermediate and stable terminal cleavage fragments and is associated with complex modulation and progressive loss of native antigenic expressions. Early in association with progressive plasmin cleavage, a stable cleavage-associated neoantigen, present in the D-fragment region of the molecule, is exposed in vitro and can be recognized by competitive inhibition radioimmunoassay with specific antiserum. It is demonstrated that there is an approximate equimolar expression of the cleavage-associated neoantigen. fg-Dneo, on the X-, Y-, and D-fragments and no recognizable (< 10-3) expression by fibrinogen or by the E-fragment. The X-fragment contains two D regions in respect to total D-fragment-associated antigenic expressions but unitary expression of fg-Dneo is observed. The Y-fragment appears to contain one D-fragment region in respect to total D-fragment-associated antigens and exhibits close to unitary expression of fg-Dneo. Terminal cleavage digests containing the D- and E-fragments exhibit more than 10-fold greater native fibrinogen antigenic expression than the sum of the constituent fragments. This suggests the presence of a non-covalently associated native complex of the D- and E-fragments, and implies contiguity of the D- and E-fragments in the native fibrinogen molecule. The cleavage-associated neoantigen, fg-Dneo, is also generated in vivo and is generically demonstrable in the plasma of patients with various forms of in vivo fibrinolysis.

Authors

Edward Plow, Thomas S. Edgington