AUTOREACTIVE T-CELLS IN GOODPASTURES-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 patien t autoreactive to alpha 3 type IV collagen of glomerular basement memb rane. 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-restrict ion were analyzed. T-cell clones specific for the alpha 3(N) NC1 domai n were established in two Goodpasture patients, but not in controls. O ne 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-t erminal area of the alpha 3(IV) NC1 domain (AA 51 to 59: GSPATWTTR). W e conclude that autoreactive T-cells exists in Goodpasture patients an d may play a crucial role in the inflammatory process. T-cell clones a re 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-bi nding site.