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A Novel HLA-DRB1*10...
A Novel HLA-DRB1*10:01-Restricted T Cell Epitope From Citrullinated Type II Collagen Relevant to Rheumatoid Arthritis
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- Chemin, Karine (author)
- Karolinska Institutet
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- Pollastro, Sabrina (author)
- Amsterdam Rheumatol & Immunol Ctr, Amsterdam, Netherlands.;Univ Amsterdam, Acad Med Ctr, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
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- James, Eddie (author)
- Virginia Mason, Benaroya Res Inst, Seattle, WA USA.
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- Ge, Changrong (author)
- Karolinska Institutet
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- Albrecht, Inka (author)
- Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden.
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- Herrath, Jessica (author)
- Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden.
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- Gerstner, Christina (author)
- Karolinska Institutet
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Tandre, Karolina (author)
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- Rizzi, Thais Sampaio (author)
- Amsterdam Rheumatol & Immunol Ctr, Amsterdam, Netherlands.;Univ Amsterdam, Acad Med Ctr, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
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- Rönnblom, Lars (author)
- Uppsala universitet,Reumatologi
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- Catrina, Anca (author)
- Karolinska Institutet
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- Holmdahl, Rikard (author)
- Karolinska Institutet
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- Klareskog, Lars (author)
- Karolinska Institutet
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- de Vries, Niek (author)
- Amsterdam Rheumatol & Immunol Ctr, Amsterdam, Netherlands.;Univ Amsterdam, Acad Med Ctr, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
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- Malmstrom, Vivianne (author)
- Karolinska Institutet
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Karolinska Institutet Amsterdam Rheumatol & Immunol Ctr, Amsterdam, Netherlands;Univ Amsterdam, Acad Med Ctr, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. (creator_code:org_t)
- Wiley, 2016
- 2016
- English.
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In: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 68:5, s. 1124-1135
- Related links:
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https://urn.kb.se/re...
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Abstract
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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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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show more...
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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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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Rheumatology and ...
- Articles in the publication
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Arthritis & Rheu ...
- By the university
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Uppsala University
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Karolinska Institutet