A FUNCTIONAL-ANALYSIS OF THE ANTIGENICITY OF STREPTOKINASE USING MONOCLONAL-ANTIBODY MAPPING AND RECOMBINANT STREPTOKINASE FRAGMENTS

Streptokinase (SK), a bacterial product of pathogenic Streptococcus sp ecies, is now widely used as an effective therapy for the treatment of heart attacks. Because naturally occurring antibody to SK is ubiquito us, serious allergic reactions to SK therapy are common. To begin to i dentify regions of the molecule that are important for the antigenicit y of SK we performed studies using a panel of 51 hybridomas producing anti-SK antibodies, recombinant SK fragments, and assays of SK activit y. Antibodies generated from mice hyperimmunized with wild-type SK wer e shown to fall into six distinct complementation groups by competitiv e binding studies. Recombinant SK fragments were used to determine the peptide regions recognized by these complementation groups. Correlati on of the effects of the mAb on SK function, with knowledge of their S K fragment-binding pattern, suggested regions of the SK molecule that are important for the construction and the catalytic function of the S K-plasminogen activator complex.