Autoreactive T-cells in Goodpasture's syndrome recognize the N-terminal NC1 domain on alpha 3 type IV collagen.
Goodpasture's syndrome is mediated by immunopathogenic autoantibodies to the alpha 3 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 alpha 3 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 alpha 3 (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 V beta 5.1. chain. This clone specifically recognized a motif at the N-terminal area of the alpha 3 (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 alpha 3 (IV) NC1 domain. At least for one of the clones, the T-cell epitope is different from the putative antibody-binding site.
Merkel
F
F
Medizinische Klinik IV, University of Erlangen-Nürnberg, Germany.
Kalluri
R
R
Marx
M
M
Enders
U
U
Stevanovic
S
S
Giegerich
G
G
Neilson
E G
EG
Rammensee
H G
HG
Hudson
B G
BG
Weber
M
M
D000595:Amino Acid Sequence; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001483:Base Sequence; D002999:Clone Cells / Q000737:chemistry / Q000276:immunology; D003094:Collagen / Q000737:chemistry / Q000276:immunology*; D018604:Epitope Mapping; D006801:Humans; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D013601:T-Lymphocytes / Q000276:immunology*
D001324:Autoantigens; D003094:Collagen