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Memory T cells spec...
Memory T cells specific to citrullinated alpha-enolase are enriched in the rheumatic joint
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- Pieper, Jennifer (author)
- Karolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Med Solna,Rheumatol Unit, Stockholm, Sweden.
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- Dubnovitsky, Anatoly (author)
- 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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- Gerstner, Christina (author)
- Karolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Med Solna,Rheumatol Unit, Stockholm, Sweden.
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- James, Eddie A. (author)
- Virginia Mason, BRI, Tetramer Core, Seattle, WA USA.
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- Rieck, Mary (author)
- Virginia Mason, BRI, Translat Res Program, Seattle, WA USA.
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- Kozhukh, Genadiy (author)
- 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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- Tandre, Karolina (author)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab
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- Pellegrino, Sara (author)
- Univ Milan, Sez Chim Gen & Organ, Dipartimento Sci Farmaceut, DISFARM, Milan, Italy.
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- Gebe, John A. (author)
- Virginia Mason, BRI, Translat Res Program, Seattle, WA USA.
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- Rönnblom, Lars (author)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab
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- Sandalova, Tatyana (author)
- Karolinska Inst, Dept Med Solna, Sci Life Lab, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden.
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- Kwok, William W. (author)
- Virginia Mason, BRI, Translat Res Program, Seattle, WA USA.
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- Klareskog, Lars (author)
- Karolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Med Solna,Rheumatol Unit, Stockholm, Sweden.
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- Buckner, Jane H. (author)
- Virginia Mason, BRI, Translat Res Program, Seattle, WA USA.
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- Achour, Adnane (author)
- Karolinska Inst, Dept Med Solna, Sci Life Lab, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden.
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- Malmström, Vivianne (author)
- Karolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Med Solna,Rheumatol Unit, Stockholm, Sweden.
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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. (creator_code:org_t)
- ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2018
- 2018
- English.
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In: Journal of Autoimmunity. - : ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD. - 0896-8411 .- 1095-9157. ; 92, s. 47-56
- Related links:
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https://www.ncbi.nlm...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- Autoimmunity
- Citrullination
- Crystal structure
- HLA class II tetramers
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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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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show more...
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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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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
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Journal of Autoi ...
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Uppsala University