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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 ...

  • Wiley,2016
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-297800
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-297800URI
  • https://doi.org/10.1002/art.39553DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:133495847URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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 ...)

  • Pollastro, SabrinaAmsterdam Rheumatol & Immunol Ctr, Amsterdam, Netherlands.;Univ Amsterdam, Acad Med Ctr, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. (author)
  • James, EddieVirginia Mason, Benaroya Res Inst, Seattle, WA USA. (author)
  • Ge, ChangrongKarolinska Institutet (author)
  • Albrecht, InkaKarolinska Univ Hosp, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden. (author)
  • Herrath, JessicaKarolinska Univ Hosp, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden. (author)
  • Gerstner, ChristinaKarolinska Institutet (author)
  • Tandre, Karolina (author)
  • Rizzi, Thais SampaioAmsterdam Rheumatol & Immunol Ctr, Amsterdam, Netherlands.;Univ Amsterdam, Acad Med Ctr, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. (author)
  • Rönnblom, LarsUppsala universitet,Reumatologi(Swepub:uu)larsronn (author)
  • Catrina, AncaKarolinska Institutet (author)
  • Holmdahl, RikardKarolinska Institutet (author)
  • Klareskog, LarsKarolinska Institutet (author)
  • de Vries, NiekAmsterdam Rheumatol & Immunol Ctr, Amsterdam, Netherlands.;Univ Amsterdam, Acad Med Ctr, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. (author)
  • Malmstrom, VivianneKarolinska Institutet (author)
  • Karolinska InstitutetAmsterdam Rheumatol & Immunol Ctr, Amsterdam, Netherlands.;Univ Amsterdam, Acad Med Ctr, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. (creator_code:org_t)

Related titles

  • In:Arthritis & Rheumatology: Wiley68:5, s. 1124-11352326-51912326-5205

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