Molecular mapping of the Goodpasture's epitope for glomerulonephritis

Goodpasture's syndrome is an autoimmune disease characterized by pulmonary hemorrhage, glomerulonephritis, and antiglomerular basement membrane (GBM) antibodies. We have studied a rat model with chimeric proteins (CPs) consisting of portions of the nephritogenic non-collagenous domain of alpha3 type IV collagen (alpha3(IV)NC1) and non-nephritogenic alpha1(IV)NC1. CPs with aminoterminal alpha3 that contains the major epitope for Goodpasture antibody binding induced EAG. We next immunized with D3, an alpha1(IV)NC1 CP with 69AA of alpha3(IV)NC1 (binds Goodpasture sera), D4, the D3 construct shortened by 4 AA (nonbinding), P9 and P10, single AA mutants (nonbinding) and S2, an alpha1(IV)NC1 with nine AA of alpha3(IV)NC1 (binding). GBM, S2 and D3 induced EAG. GBM immunized rats had intense IgG deposits but S2 and D3 rats had minimal deposits. A 13 mer rat peptide encompassing the aminoterminal site induced EAG sans antibody, while peptides not encompassing the region failed to induce GN. Asparagine at position 19 rather than isoleucine was essential for disease induction. These studies define critical limited AA sequences of alpha3(IV)NC1 associated with glomerulonephritis without antibody, and demonstrate that this region contains a T-cell epitope responsible for induction of glomerulonephritis.

Chen, Lanlin (author)
Hellmark, ThomasLund University,Lunds universitet,Njurmedicin,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Autoimmunitet och njursjukdomar,Forskargrupper vid Lunds universitet,Nephrology,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Autoimmunity and kidney diseases,Lund University Research Groups(Swepub:lu)njur-the (author)
Fox, Jay (author)
Wieslander, JörgenLund University,Lunds universitet,Njurmedicin,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Nephrology,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)njur-jwi (author)
NjurmedicinSektion II (creator_code:org_t)

In:Transactions of the American Clinical and Climatological Association116, s. 229-2380065-7778

By the author/editor: Bolton, W Kline; Chen, Lanlin; Hellmark, Thomas; Fox, Jay; Wieslander, Jörg ...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Urology and Neph ...

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