PMID- 1280820 OWN - NLM STAT- MEDLINE DCOM- 19930107 LR - 20190501 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 89 IP - 23 DP - 1992 Dec 1 TI - Identification of a pathogenic epitope involved in initiation of Heymann nephritis. PG - 11179-83 AB - 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. FAU - Kerjaschki, D AU - Kerjaschki D AD - Section of Ultrastructural Pathology and Cell Biology, University of Vienna, Austria. FAU - Ullrich, R AU - Ullrich R FAU - Diem, K AU - Diem K FAU - Pietromonaco, S AU - Pietromonaco S FAU - Orlando, R A AU - Orlando RA FAU - Farquhar, M G AU - Farquhar MG LA - eng GR - DK17724/DK/NIDDK NIH HHS/United States GR - NSO7078-13/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Autoantibodies) RN - 0 (Epitopes) RN - 0 (Heymann Nephritis Antigenic Complex) RN - 0 (Membrane Glycoproteins) RN - 0 (Recombinant Proteins) SB - IM MH - Animals MH - Autoantibodies/immunology MH - Blotting, Western MH - DNA Mutational Analysis MH - Epitopes MH - Glomerulonephritis/*immunology MH - Heymann Nephritis Antigenic Complex MH - Immunization, Passive MH - Kidney Glomerulus/immunology MH - Membrane Glycoproteins/chemistry/*immunology MH - Rats MH - Recombinant Proteins/immunology MH - Sequence Deletion PMC - PMC50513 EDAT- 1992/12/01 00:00 MHDA- 1992/12/01 00:01 PMCR- 1993/06/01 CRDT- 1992/12/01 00:00 PHST- 1992/12/01 00:00 [pubmed] PHST- 1992/12/01 00:01 [medline] PHST- 1992/12/01 00:00 [entrez] PHST- 1993/06/01 00:00 [pmc-release] AID - 10.1073/pnas.89.23.11179 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11179-83. doi: 10.1073/pnas.89.23.11179.