Lupus-derived autoantibodies with dual autoactivity: anti-DNA and anti-Fc. II. Fine specificity of anti-self autoreactivity

Abstract

The anti-immunoglobulin reactivity of two monoclonal, dual specific, autoantibodies, BV 17-45 and BV 04-01 was examined. The current study further defined the anti-immunoglobulin autoreactivity of these MoAbs to be Fc-specific. Both BV 17-45 and BV 04-01 bound their own Fc domains in addition to Fc regions of other MoAbs of similar isotype with varying levels of activity. The different anti-Fc reactivity patterns of BV 17-45 and BV 04-01 suggested that these MoAbs recognized distinct epitopes. Neither BV 17-45 nor BV 04-01 bound Fab fragments or single-chain antibody derivatives, which confirmed that the anti-immunoglobulin reactivity of these autoantibodies was Fc-specific. In addition, abrogation of anti-Fc reactivity was observed when affinity-labelled MoAbs were used as coating antigens in solid-phase ELISAs. These results implied that active-site ligand binding induced conformational changes which altered the Fc epitope(s) recognized by BV 17-45 and BV 04-01.