title: Autoreactive T-cells in Goodpasture's syndrome recognize the N-terminal NC1 domain on alpha 3 type IV collagen.
abstract: 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.
authors.affiliation: Medizinische Klinik IV, University of Erlangen-Nürnberg, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Merkel
authors.forename: R
authors.initials: R
authors.lastname: Kalluri
authors.forename: M
authors.initials: M
authors.lastname: Marx
authors.forename: U
authors.initials: U
authors.lastname: Enders
authors.forename: S
authors.initials: S
authors.lastname: Stevanovic
authors.forename: G
authors.initials: G
authors.lastname: Giegerich
authors.forename: E G
authors.initials: EG
authors.lastname: Neilson
authors.forename: H G
authors.initials: HG
authors.lastname: Rammensee
authors.forename: B G
authors.initials: BG
authors.lastname: Hudson
authors.forename: M
authors.initials: M
authors.lastname: Weber
mesh_terms: 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*
chemical_list: D001324:Autoantigens; D003094:Collagen