ISOLATION OF CDNAS ENCODING IMMUNOGENIC REGIONS OF GP330, THE AUTOANTIGEN INVOLVED IN HEYMANN NEPHRITIS

Active Heymann nephritis is an organ-specific autoimmune disease of th e rat kidney, characterized by the formation of immune complexes locat ed subepithelially in the glomerulus. The T cell-mediated humoral immu ne response is directed to gp330, a large renal epithelial glycoprotei n which is expressed both in the proximal tubule and on glomerular pod ocytes. In this study polyclonal rabbit antibodies raised against affi nity-purified rat gp330 were used to screen a lambda-gt11 expression l ibrary of the rat kidney. One cDNA clone that was recognized by the an tibodies coded for a 2.7-kb protein that is not described in the seque nce database of GenBank/EMBL. Two other groups of cDNA clones were ide ntified that displayed similarity with several members of the low-dens ity lipoprotein (LDL)-receptor gene family to which gp330 belongs. By comparison with the gp330-cDNA sequence, these two clones could be map ped to two remote areas on the extracellular domain of gp330. The anti genicity of these two areas is in accordance with their location in hi ghly hydrophilic regions on the extracellular domain of gp330. The cDN A clones described in this study may represent two main immunodominant regions on rat gp330.