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  • Pieper, JenniferKarolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Med Solna,Rheumatol Unit, Stockholm, Sweden. (author)

Memory T cells specific to citrullinated alpha-enolase are enriched in the rheumatic joint

  • Article/chapterEnglish2018

Publisher, publication year, extent ...

  • ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD,2018
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-364924
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-364924URI
  • https://doi.org/10.1016/j.jaut.2018.04.004DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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

Notes

  • ACPA-positive rheumatoid arthritis (RA) is associated with distinct HLA-DR alleles and immune responses to many citrullinated self-antigens. Herein we investigated the T cell epitope confined within alpha-enolase(326-340) in the context of HLA-DRB1*04:01 and assessed the corresponding CD4(+) T cells in both the circulation and in the rheumatic joint. Comparative crystallographic analyses were performed for the native and citrullinated alpha-enolase(326-340) peptides in complex with HLA-DRB1*04:01. HLA-tetramers assembled with either the native or citrullinated peptide were used for ex vivo and in vitro assessment of a enolase-specific T cells in peripheral blood, synovial fluid and synovial tissue by flow cytometry. The native and modified peptides take a completely conserved structural conformation within the peptide binding cleft of HLA-DRB1*04:01. The citrulline residue-327 was located N-terminally, protruding towards TCRs. The frequencies of T cells recognizing native eno(326-340) were similar in synovial fluid and peripheral blood, while in contrast, the frequency of T cells recognizing cit-eno(326-340) was significantly elevated in synovial fluid compared to peripheral blood (3.6-fold, p = 0.0150). Additionally, citrulline-specific T cells with a memory phenotype were also significantly increased (1.6-fold, p = 0.0052) in synovial fluid compared to peripheral blood. The native T cell epitope confined within alpha-enolase(326-340) does not appear to lead to complete negative selection of cognate CD4(+) T cells. In RA patient samples, only T cells recognizing the citrullinated version of alpha-enolase(326-340) were found at elevated frequencies implicating that neo-antigen formation is critical for breach of tolerance. (C) 2018 Elsevier Ltd. All rights reserved.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Dubnovitsky, AnatolyKarolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Med Solna,Rheumatol Unit, Stockholm, Sweden.;Karolinska Inst, Dept Med Solna, Sci Life Lab, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden. (author)
  • Gerstner, ChristinaKarolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Med Solna,Rheumatol Unit, Stockholm, Sweden. (author)
  • James, Eddie A.Virginia Mason, BRI, Tetramer Core, Seattle, WA USA. (author)
  • Rieck, MaryVirginia Mason, BRI, Translat Res Program, Seattle, WA USA. (author)
  • Kozhukh, GenadiyKarolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Med Solna,Rheumatol Unit, Stockholm, Sweden.;Karolinska Inst, Dept Med Solna, Sci Life Lab, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden. (author)
  • Tandre, KarolinaUppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)karotand (author)
  • Pellegrino, SaraUniv Milan, Sez Chim Gen & Organ, Dipartimento Sci Farmaceut, DISFARM, Milan, Italy. (author)
  • Gebe, John A.Virginia Mason, BRI, Translat Res Program, Seattle, WA USA. (author)
  • Rönnblom, LarsUppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)larsronn (author)
  • Sandalova, TatyanaKarolinska Inst, Dept Med Solna, Sci Life Lab, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden. (author)
  • Kwok, William W.Virginia Mason, BRI, Translat Res Program, Seattle, WA USA. (author)
  • Klareskog, LarsKarolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Med Solna,Rheumatol Unit, Stockholm, Sweden. (author)
  • Buckner, Jane H.Virginia Mason, BRI, Translat Res Program, Seattle, WA USA. (author)
  • Achour, AdnaneKarolinska Inst, Dept Med Solna, Sci Life Lab, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden. (author)
  • Malmström, VivianneKarolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Med Solna,Rheumatol Unit, Stockholm, Sweden. (author)
  • Karolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Med Solna,Rheumatol Unit, Stockholm, Sweden.Karolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Med Solna,Rheumatol Unit, Stockholm, Sweden.;Karolinska Inst, Dept Med Solna, Sci Life Lab, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden. (creator_code:org_t)

Related titles

  • In:Journal of Autoimmunity: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD92, s. 47-560896-84111095-9157

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