Identification of novel human aggrecan T cell epitopes in HLA-B27 transgenic mice associated with spondyloarthropathy
The pathology of ankylosing spondylitis, reactive arthritis, and other spondyloarthropathies (SpA) is closely associated with the human leukocyte class I Ag HLA-B27. A characteristic finding in SpA is inflammation of cartilage structures of the joint, in particular at the site of ligament/tendon and bone junction (enthesitis). In this study, we investigated the role of CD8+ T cells in response to the cartilage proteoglycan aggrecan as a potential candidate autoantigen in BALB/c-B27 transgenic mice. We identified four new HLA-B27-restricted nonamer peptides, one of them (no. 67) with a particularly strong T cell immunogenicity. Peptide no. 67 immunization was capable of stimulating HLA-B27-restricted, CD8+ T cells in BALB/c-B27 transgenic animals, but not in wild-type BALB/c mice. The peptide was specifically recognized on P815-B27 transfectants by HLA-B27-restricted CTLs, which were also detectable by HLA tetramer staining ex vivo as well as in situ. Most importantly, analysis of the joints from peptide no. 67-immunized mice induced typical histological signs of SpA. Our data indicate that HLA-B27-restricted epitopes derived from human aggrecan are involved in the induction of inflammation (tenosynovitis), underlining the importance of HLA-B27 in the pathogenesis of SpA.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2004 |
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| Erschienen: |
2004 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:173 |
|---|---|
| Enthalten in: |
Journal of immunology (Baltimore, Md. : 1950) - 173(2004), 8 vom: 15. Okt., Seite 4859-66 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kuon, Wolfgang [VerfasserIn] |
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| Themen: |
Acan protein, mouse |
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| Anmerkungen: |
Date Completed 03.11.2004 Date Revised 10.12.2019 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM151427593 |
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| 041 | |a eng | ||
| 100 | 1 | |a Kuon, Wolfgang |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Identification of novel human aggrecan T cell epitopes in HLA-B27 transgenic mice associated with spondyloarthropathy |
| 264 | 1 | |c 2004 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 03.11.2004 | ||
| 500 | |a Date Revised 10.12.2019 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The pathology of ankylosing spondylitis, reactive arthritis, and other spondyloarthropathies (SpA) is closely associated with the human leukocyte class I Ag HLA-B27. A characteristic finding in SpA is inflammation of cartilage structures of the joint, in particular at the site of ligament/tendon and bone junction (enthesitis). In this study, we investigated the role of CD8+ T cells in response to the cartilage proteoglycan aggrecan as a potential candidate autoantigen in BALB/c-B27 transgenic mice. We identified four new HLA-B27-restricted nonamer peptides, one of them (no. 67) with a particularly strong T cell immunogenicity. Peptide no. 67 immunization was capable of stimulating HLA-B27-restricted, CD8+ T cells in BALB/c-B27 transgenic animals, but not in wild-type BALB/c mice. The peptide was specifically recognized on P815-B27 transfectants by HLA-B27-restricted CTLs, which were also detectable by HLA tetramer staining ex vivo as well as in situ. Most importantly, analysis of the joints from peptide no. 67-immunized mice induced typical histological signs of SpA. Our data indicate that HLA-B27-restricted epitopes derived from human aggrecan are involved in the induction of inflammation (tenosynovitis), underlining the importance of HLA-B27 in the pathogenesis of SpA | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Acan protein, mouse |2 NLM | |
| 650 | 7 | |a Aggrecans |2 NLM | |
| 650 | 7 | |a Epitopes, T-Lymphocyte |2 NLM | |
| 650 | 7 | |a Extracellular Matrix Proteins |2 NLM | |
| 650 | 7 | |a HLA-B27 Antigen |2 NLM | |
| 650 | 7 | |a Lectins, C-Type |2 NLM | |
| 650 | 7 | |a Proteoglycans |2 NLM | |
| 700 | 1 | |a Kuhne, Maren |e verfasserin |4 aut | |
| 700 | 1 | |a Busch, Dirk H |e verfasserin |4 aut | |
| 700 | 1 | |a Atagunduz, Pamir |e verfasserin |4 aut | |
| 700 | 1 | |a Seipel, Martina |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Peihua |e verfasserin |4 aut | |
| 700 | 1 | |a Morawietz, Lars |e verfasserin |4 aut | |
| 700 | 1 | |a Fernahl, Gabriele |e verfasserin |4 aut | |
| 700 | 1 | |a Appel, Heiner |e verfasserin |4 aut | |
| 700 | 1 | |a Weiss, Elisabeth H |e verfasserin |4 aut | |
| 700 | 1 | |a Krenn, Veit |e verfasserin |4 aut | |
| 700 | 1 | |a Sieper, Joachim |e verfasserin |4 aut | |
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