EXPERIMENTAL ANTI‐GBM GLOMERULONEPHRITIS INDUCED IN RATS BY IMMUNIZATION WITH SYNTHETIC PEPTIDES BASED ON SIX α CHAINS OF HUMAN TYPE IV COLLAGEN

The anti-glomerular basement membrane (GBM)-nephritis-inducing activity of six synthetic peptides having an amino acid sequence consisting of the six α chains of human type IV collagen was examined by injecting the peptides into rats. The peptides consisted of 27 amino acid residues from the non-collagenous domain (NCl) of the α1 to α6 chains and were non-consensus sequences sandwiched between two consensus sequences near the carboxyl terminus. Each peptide was coupled to keyhole limpet haemocyanin and injected with adjuvant into the footpads of 20 female WKY/NCrj rats. The number of rats with proteinuria (over 10.0 mg of urinary protein/15 h) and haematuria was 2 with the α3 peptide, 8 with the α4 peptide, and 1 with the α5 peptide. Histological changes seen in the glomeruli were characteristic of those in anti-GBM nephritis. Linear deposition of rat IgG along the GBM was observed in five rats injected with the α4 peptide. A nephritogenic monoclonal antibody against the α4 peptide was established using lymph node cells from a rat injected with the α4 peptide. The results indicate that α4(IV)NC1 is a potent nephritogenic antigen like α3(IV)NC1, which has already been recognized as a primary target antigen in Goodpasture's syndrome.