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A Novel HLA-DRB1*10...
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Chemin, KarineKarolinska Institutet
(author)
A Novel HLA-DRB1*10:01-Restricted T Cell Epitope From Citrullinated Type II Collagen Relevant to Rheumatoid Arthritis
- Article/chapterEnglish2016
Publisher, publication year, extent ...
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Wiley,2016
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printrdacarrier
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LIBRIS-ID:oai:DiVA.org:uu-297800
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-297800URI
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https://doi.org/10.1002/art.39553DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:133495847URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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Objective. Antibodies against citrullinated type II collagen (Cit-CII) are common in the sera and synovial fluid of patients with rheumatoid arthritis (RA); however, the known T cell epitope of CII is not dependent on citrullination. The aim of this study was to identify and functionally characterize the Cit-CII-restricted T cell epitopes that are relevant to RA. Methods. Peripheral blood mononuclear cells (PBMCs) from HLA-DRB1*10:01-positive patients with RA and healthy donors were stimulated in vitro with candidate CII peptides. CD154 up-regulation was measured as a marker of antigen-specific activation, and anti-HLA-DR-blocking experiments confirmed HLA restriction. Cytokine production was measured using a Luminex technique. Direct peptide-binding assays using HLA-DRB1*10:01 and HLA-DRB1*04:01 monomeric proteins were performed. The T cell receptor (TCR) beta-chain of CD154-enriched antigen-specific T cells was analyzed using high-throughput sequencing. Results. A novel Cit-CII peptide was identified based on its ability to activate CD4+ T cells from HLA-DRB1*10:01-positive individuals. When stimulated in vitro, Cit-CII autoreactive T cells produced proinflammatory cytokines. Cit-CII311-325 bound (with low affinity) to HLA-DRB1*10:01 but not to HLA-DRB1*04:01, while the native form was unable to bind either protein. In addition, highly expanded clones were identified in the TCR beta repertoire of Cit-CII311-325-stimulated PBMCs. Conclusion. These results illustrate the ability of the citrullination process to create T cell epitopes from CII, a cartilage-restricted protein that is relevant to RA pathogenesis. The exclusive binding of Cit-CII311-325 to HLA-DRB1*10:01 suggests that recognition of citrullinated epitopes might vary between individuals carrying different RA-associated HLA-DR molecules.
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Added entries (persons, corporate bodies, meetings, titles ...)
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Pollastro, SabrinaAmsterdam Rheumatol & Immunol Ctr, Amsterdam, Netherlands.;Univ Amsterdam, Acad Med Ctr, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
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James, EddieVirginia Mason, Benaroya Res Inst, Seattle, WA USA.
(author)
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Ge, ChangrongKarolinska Institutet
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Albrecht, InkaKarolinska Univ Hosp, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden.
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Herrath, JessicaKarolinska Univ Hosp, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden.
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Gerstner, ChristinaKarolinska Institutet
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Tandre, Karolina
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Rizzi, Thais SampaioAmsterdam Rheumatol & Immunol Ctr, Amsterdam, Netherlands.;Univ Amsterdam, Acad Med Ctr, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
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Rönnblom, LarsUppsala universitet,Reumatologi(Swepub:uu)larsronn
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Catrina, AncaKarolinska Institutet
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Holmdahl, RikardKarolinska Institutet
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Klareskog, LarsKarolinska Institutet
(author)
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de Vries, NiekAmsterdam Rheumatol & Immunol Ctr, Amsterdam, Netherlands.;Univ Amsterdam, Acad Med Ctr, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
(author)
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Malmstrom, VivianneKarolinska Institutet
(author)
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Karolinska InstitutetAmsterdam Rheumatol & Immunol Ctr, Amsterdam, Netherlands.;Univ Amsterdam, Acad Med Ctr, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
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In:Arthritis & Rheumatology: Wiley68:5, s. 1124-11352326-51912326-5205
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Chemin, Karine
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Pollastro, Sabri ...
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James, Eddie
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Ge, Changrong
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Albrecht, Inka
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Herrath, Jessica
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Gerstner, Christ ...
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Tandre, Karolina
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Rizzi, Thais Sam ...
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Rönnblom, Lars
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Catrina, Anca
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Holmdahl, Rikard
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Klareskog, Lars
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de Vries, Niek
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Malmstrom, Vivia ...
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