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Memory T cells spec...
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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 ...
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ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD,2018
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-364924
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-364924URI
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https://doi.org/10.1016/j.jaut.2018.04.004DOI
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
Notes
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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.
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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.
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Gerstner, ChristinaKarolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Med Solna,Rheumatol Unit, Stockholm, Sweden.
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James, Eddie A.Virginia Mason, BRI, Tetramer Core, Seattle, WA USA.
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Rieck, MaryVirginia Mason, BRI, Translat Res Program, Seattle, WA USA.
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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.
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Tandre, KarolinaUppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)karotand
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Pellegrino, SaraUniv Milan, Sez Chim Gen & Organ, Dipartimento Sci Farmaceut, DISFARM, Milan, Italy.
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Gebe, John A.Virginia Mason, BRI, Translat Res Program, Seattle, WA USA.
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Rönnblom, LarsUppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)larsronn
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Sandalova, TatyanaKarolinska Inst, Dept Med Solna, Sci Life Lab, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden.
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Kwok, William W.Virginia Mason, BRI, Translat Res Program, Seattle, WA USA.
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Klareskog, LarsKarolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Med Solna,Rheumatol Unit, Stockholm, Sweden.
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Buckner, Jane H.Virginia Mason, BRI, Translat Res Program, Seattle, WA USA.
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Achour, AdnaneKarolinska Inst, Dept Med Solna, Sci Life Lab, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden.
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Malmström, VivianneKarolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Med Solna,Rheumatol Unit, Stockholm, Sweden.
(author)
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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.
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In:Journal of Autoimmunity: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD92, s. 47-560896-84111095-9157
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Pieper, Jennifer
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Dubnovitsky, Ana ...
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Gerstner, Christ ...
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James, Eddie A.
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Rieck, Mary
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Kozhukh, Genadiy
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Tandre, Karolina
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Pellegrino, Sara
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Gebe, John A.
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Rönnblom, Lars
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Sandalova, Tatya ...
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Kwok, William W.
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Klareskog, Lars
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Buckner, Jane H.
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Achour, Adnane
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Malmström, Vivia ...
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