| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Research Abstract |
Heymann nephritis is an experimental model of human idiopathic membranous nephropathy. As Heymann nephritis can be induced by immunizing rats with proteins derived from renal tubule, there have been many attempts to isolate and characterize a nephrito- genic antigen from crude mixes of brush border antigens.
Kerjaschki et al. demonstrated that a nephritogenic 330-kD glycoprotein (gp330). presented in the brush border of renal proximal tubule as well as on the glomerular epithelial surface, and proposed that Heymann nephritis is caused by locally formed. antigen-antibody complexes on the epithelial surface of glome- rulus (in situ immune complex formation theory), rather than the deposition of circulating immune complex.
We have isolated a nephritogenic 120-kD (gp120) antigen from rat tubule brush border. The gpl20 induces rat Heymann nephritis. A monoclonal antibody to the antigen reacted exclusively with the brush border, not with glomerular epithelia on direct immunofluorescence and immunoelectron microscopy.
cDNA cloning and sequencing of the nephritogenic. Gp120 antigen showed similarity to that of low density lipoprotein receptor (LDLR) which was also reported as a homologue of gp330 antigen.
Nephritogenic major epitope in gp330 has been reported to localize in aminoacids 1160-1205 on LDLR, whereas, our gp120 antigen localizes in aminoacids approximately between 1534- 2910.
As we have obtained enough cDNA data for our gp120 antigen, we are preparing several bacterial recombinant proteins. Using these recombinant proteins, we can confirm which part is antigenic, and will enable us to select the most important region in gp120 antigen.
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