Identification of a pathogenic epitope involved in initiation of Heymann nephritis.
Heymann nephritis is an experimental autoimmune disease model for human membranous nephropathy. We have recently identified a pathogenic epitope, clone 14 (C14), responsible for formation and deposition of glomerular immune complexes that is contained within the small subunit of the Heymann nephritis antigenic complex (HNAC). HNAC is a heterodimer composed of a large subunit designated gp330 and a smaller (44 kDa) subunit, which is immunologically identical to the receptor-associated protein. In this study, we prepared antibodies to fusion proteins with C-terminal deletions in the C14 sequence and assessed their ability to promote formation of immune deposits (IDs). When IgG specific for the shortest truncated fusion protein (C14/delta 3; 86 amino acids) was injected into rats, small IDs developed. In contrast, when IgG raised against the full-length C14 sequence was depleted of its reactivity toward the C14/delta 3 fusion protein (C14/delta 3-fp), no IDs could be detected. These data indicate that at least one pathogenic epitope is contained within the N-terminal 86 amino acids of C14. Since the IDs induced with the C14/delta 3-fp-specific IgG are smaller than those induced with the poly-epitope-specific anti-gp330 antibodies, it is likely that other epitopes in addition to those expressed by the C14/delta 3-fp are required for formation and growth of immune complexes.
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D015153:Blotting, Western; D004252:DNA Mutational Analysis; D000939:Epitopes; D005921:Glomerulonephritis / Q000276:immunology*; D026541:Heymann Nephritis Antigenic Complex; D007116:Immunization, Passive; D007678:Kidney Glomerulus / Q000276:immunology; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000276:immunology*; D051381:Rats; D011994:Recombinant Proteins / Q000276:immunology; D017384:Sequence Deletion
D001323:Autoantibodies; D000939:Epitopes; D026541:Heymann Nephritis Antigenic Complex; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins