A small N-terminal 60-kD fragment of gp600 (megalin), the major autoantigen of active Heymann nephritis, can induce a full-blown disease

Andrew V. Oleinikov, Brady J. Feliz, Sudesh P Makker

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Active Heymann nephritis of rat, an autoimmune glomerular disease, is an immunohistological, ultrastructural, and clinical model of human membranous glomerulonephritis. Both diseases in their full-blown form are characterized by (1) the formation of large, subepithelial glomerular immune deposits, which stain for IgG, C3, and membrane attack (C5b-9) components of complement and (2) the excretion of large amounts of protein in the urine (proteinuria). The target autoantigen of active Heymann nephritis is a large transmembrane renal glycoprotein with a molecular weight of approximately 600 kD, variously named gp600, gp330, LRP-2, or 'megalin'. This study was performed to identify the region in this enormously large glycoprotein that would produce full- blown active Heymann nephritis. A stable, small (60-kD) proteolytic fragment of gp600 was isolated and localized to the N-terminal end of the molecule using Western blot, sequencing, and amino acid analyses. Based on its primary structure, this fragment contains approximately 60 cysteine residues, the cross-linking of which to each other probably explains its stability. Immunization of rats with this fragment induced a full-blown disease that was comparable to the disease induced by a preparation containing the whole protein. These results indicate that this small fragment, retaining the natural disulfide bonds and probably its overall structure, contains those B and T cell epitopes that are sufficient to produce this organ-specific autoimmune disease.

Original languageEnglish (US)
Pages (from-to)57-64
Number of pages8
JournalJournal of the American Society of Nephrology
Volume11
Issue number1
StatePublished - Jan 2000

ASJC Scopus subject areas

  • Nephrology

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