Autoreactive T-cells in Goodpasture's syndrome recognize the N-terminal NC1 domain on α3 type IV collagen

Frank Merkel, Raghuram Kalluri, Martin Marx, Uwe Enders, Stefan Stevanovic, Gerhard Giegerich, Eric G. Neilson, Hans G. Rammensee, Billy G. Hudson, Manfred Weber*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

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 languageEnglish (US)
Pages (from-to)1127-1133
Number of pages7
JournalKidney international
Volume49
Issue number4
DOIs
StatePublished - 1996

ASJC Scopus subject areas

  • Nephrology

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