LUPUS-DERIVED AUTOANTIBODIES WITH DUAL AUTOACTIVITY - ANTI-DNA AND ANTI-FC .1. COMPARISON OF IGG AUTOREACTIVITIES WITH SINGLE-CHAIN FV DERIVATIVES

Investigations into the intrinsic affinity and reactivity of autoanti- DNA active sites were initiated through the use of purified monoclonal IgG and the synthesis of single-chain Fv derivatives of murine monocl onal anti-DNA autoantibodies BV 04-01 and BV 17-45. Results showed tha t relative to the respective IgG hybridomas, only the BV 04-01 SCA der ivative showed demonstrable reactivity with DNA. The monovalent single -chain derivative of BV 17-45 showed no reactivity with DNA in solutio n or solid-phase assays, even though the parental IgG had been previou sly described as high affinity. However, 17-45 displayed reactivity as a bivalent single-chain derivative. In addition, upon concentration, BV 17-45 IgG formed a highly stable, papain-resistant precipitate. Inv estigations into the nature of the precipitate revealed that BV 17-45 possessed significant, DNA-inhibitable autobinding to its own IgG mole cule. BV 04-01 also possessed similar anti-self reactivity. Thus, both monoclonal autoantibodies examined in this study possessed dual bindi ng specificity; anti-DNA and anti-self.