Tracking the in vivo localization of streptococcal cell membrane (SCM) monoclonal antibodies: potential model for post-streptococcal sequelae.

Placement of ten different anti-streptococcal monoclonal antibody (mAb) secreting hybridoma cells, as well as positive and negative controls into animals and sacrificing on a daily basis showed a difference in the tissue sites of accumulating mAb as noted by fluorescent antibody testing. Initial binding of the mAb was noted by day two on the kidney GBM in all the animals. Striated muscle tissues tested positive starting at day nine with only four of the mAbs, by which time the GBM was strongly positive. Fluorescent antibody testing of heart and skeletal muscle from animals in which one of the polyreactive IgM mAb secreting hybridoma cell lines was placed showed a distinctive staining of the Z-lines. Indirect fluorescent and immunoperoxidase testing as well as competitive blocking experiments confirmed the reactivity of this mAb for the Z-line of heart and skeletal muscle. Immunodots and Western blots along with direct and blocking assays confirmed that the critical cross-reactive Z-line antigen was alpha-actinin, supporting the concept that this anti-SCM mAb was reactive both in vivo and in vitro. These results confirm the cross-reactive nature of anti-SCM antibodies for mammalian tissue and bear important implications on the etiology of post-streptococcal glomerulonephritis and rheumatic heart disease.