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

doi:10.1038/ki.1996.163

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

Dean's Office

Research output: Contribution to journal › Article › peer-review

58 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 language	English (US)
Pages (from-to)	1127-1133
Number of pages	7
Journal	Kidney international
Volume	49
Issue number	4
DOIs	https://doi.org/10.1038/ki.1996.163
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

Access to Document

10.1038/ki.1996.163

Cite this

@article{34a1a6789acc4782a01a4143557affc0,

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

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.",

author = "Frank Merkel and Raghuram Kalluri and Martin Marx and Uwe Enders and Stefan Stevanovic and Gerhard Giegerich and Neilson, {Eric G.} and Rammensee, {Hans G.} and Hudson, {Billy G.} and Manfred Weber",

note = "Funding Information: 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 Funding Information: Acknowledgments This work was supported by a grant of the Deutsche Forschungs-",

year = "1996",

doi = "10.1038/ki.1996.163",

language = "English (US)",

volume = "49",

pages = "1127--1133",

journal = "Kidney international",

issn = "0085-2538",

publisher = "Elsevier B.V.",

number = "4",

}

TY - JOUR

T1 - Autoreactive T-cells in Goodpasture's syndrome recognize the N-terminal NC1 domain on α3 type IV collagen

AU - Merkel, Frank

AU - Kalluri, Raghuram

AU - Marx, Martin

AU - Enders, Uwe

AU - Stevanovic, Stefan

AU - Giegerich, Gerhard

AU - Neilson, Eric G.

AU - Rammensee, Hans G.

AU - Hudson, Billy G.

AU - Weber, Manfred

N1 - Funding Information: 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 Funding Information: Acknowledgments This work was supported by a grant of the Deutsche Forschungs-

PY - 1996

Y1 - 1996

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0029878748&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029878748&partnerID=8YFLogxK

U2 - 10.1038/ki.1996.163

DO - 10.1038/ki.1996.163

M3 - Article

C2 - 8691734

AN - SCOPUS:0029878748

SN - 0085-2538

VL - 49

SP - 1127

EP - 1133

JO - Kidney international

JF - Kidney international

IS - 4

ER -

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

Abstract

Funding

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this