Abstract
Goodpasture's syndrome is mediated by immunopathogenic autoantibodies to the α3 NC1 domain of type IV collagen. It is not known whether collaborating T-cells participate in this autoreactive response. Here we describe the first T-cell clone isolated from a Goodpasture patient autoreactive to α3 type IV collagen of glomerular basement membrane. To investigate cellular autoreactivity, T-cells from Goodpasture patients or controls were isolated and stimulated by purified native or recombinant type IV collagen proteins and synthetic oligopeptides. Cell surface markers, the T-cell receptor repertoire, and MHC-restriction were analyzed. T-cell clones specific for the α3(IV) NC1 domain were established in two Goodpasture patients, but not in controls. One of the three CD8+ T-cell clones was characterized further. It was MHC class I restricted (HLA-A11) and expressed the T-cell receptor Vβ 5.1. chain. This clone specifically recognized a motif at the N-terminal area of the α3(IV) NC1 domain (AA 51 to 59: GSPATWTTR). We conclude that autoreactive T-cells exists in Goodpasture patients and may play a crucial role in the inflammatory process. T-cell clones are autoreactive to the α3(IV) NC1 domain. At least for one of the clones, the T-cell epitope is different from the putative antibody-binding site.
Original language | English (US) |
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Pages (from-to) | 1127-1133 |
Number of pages | 7 |
Journal | Kidney international |
Volume | 49 |
Issue number | 4 |
DOIs | |
State | Published - 1996 |
Funding
gemeinschaft, SFB 263, C 6, to M.W. This study was also supported by the- following NIH grants: DK-1838t - DK-07006 DK-30380. We wish to thank PD Dr. M. Lohoff, Department of Microbiology, University of Erlangen-NUrnberg, for his support on FACS analysis and for his critical comments. We gratefully acknowledge the support of RE Acknowledgments This work was supported by a grant of the Deutsche Forschungs-
ASJC Scopus subject areas
- Nephrology