The specificity of nephritogenic antibodies. III. Binding of anti-Fx1A antibodies in glomeruli is dependent on dual specificity.

Rabbit antibodies against rat tubular brushborder antigens (Fx1A) give rise to in situ formation of immune aggregates along the glomerular capillary walls after intravenous injection into rats. These antibodies (anti-Fx1A), able to produce heterologous immune complex glomerulopathy (HIC) in the rat, have previously been shown to bind with brushborders (anti-BB) as well as with rat thymocytes (anti-T). In the present communication, this dual specificity was also demonstrated in antibodies eluted from kidneys of rats with HIC. It further appeared that, when the anti-thymocyte binding activity was selectively removed from these antibodies, using immunoabsorption with rat tissue extracts, these anti-Fx1A antibodies were no longer able to stain glomerular basement membranes (GBM) as demonstrated at the ultrastructural level using the peroxidase technique. Following perfusion of these antibodies in the normal rat kidney ex vivo, binding along the capillary walls was also below the detection level, in contrast to non anti-T depleted anti-Fx1A IgG. Biochemical analysis (including immunoblotting) showed that the anti-T moiety of anti-Fx1A was directed to a 90 kD component of Fx1A, since selective absorption of this specificity prevented staining of this 90 kD component. It is concluded, that this anti-T specificity within rabbit anti-Fx1A plays a crucial role in local immune complex formation in the rat kidney ex vivo. Whether this holds also for its role in the pathogenesis of HIC in vivo awaits further confirmation.