SLE: Unusual Recombinant Monoclonal Light Chain NGTA3-Pro-DNase Possessing Three Different Activities Trypsin-like, Metalloprotease and DNase

Objective: DNAand myelin basic protein (MBP)-hydrolyzing antibodies can play an important role in the pathogenesis of systemic lupus erythematosus (SLE), therefore their analysis seems to be important. Results: In mammalians there are serine proteases, metalloproteases, and DNases. Each of these and many other enzymes catalyze only one chemical reaction. Very unusual and unpredictable situation was revealed by us in the case of monoclonal abzymes corresponding to the sera of patients with SLE. The small pools of phage particles displaying light chains with different affinity for myelin basic protein (MBP) were isolated by affinity chromatography on MBP-Sepharose. In contrast to canonical enzymes, one of twenty five MLChs demonstrated three different enzymatic activities; it efficiently hydrolyzed MBP (but not other proteins) and DNA. Other twenty four MLChs hydrolyzed only MBP. The proteolytic activity of NGTA3-pro-DNase was efficiently inhibited by specific inhibitors of serine-like (PMSF) and metalloproteases (EDTA). Protease and DNase properties of NGTA3-pro-DNase differ significantly from those for the corresponding canonical enzymes. Conclusion: This is the first example of monoclonal antibodies with three different catalytic activities. The principal possibility of the existence of monoclonal antibodies with several different enzymatic activities is unexpected but very important for the further understanding of unknown biological functions of human