Crossreactivity to vinculin and microbes provides a molecular basis for HLA-based protection against rheumatoid arthritis
dc.contributor.author | Van Heemst, J. | en |
dc.contributor.author | Jansen, D. T. S. L. | en |
dc.contributor.author | Polydorides, Savvas | en |
dc.contributor.author | Moustakas, Antonis K. | en |
dc.contributor.author | Bax, M. | en |
dc.contributor.author | Feitsma, A. L. | en |
dc.contributor.author | Bontrop-Elferink, D. G. | en |
dc.contributor.author | Baarse, M. | en |
dc.contributor.author | Van Der Woude, D. | en |
dc.contributor.author | Wolbink, G. -J | en |
dc.contributor.author | Rispens, T. | en |
dc.contributor.author | Koning, F. | en |
dc.contributor.author | De Vries, R. R. P. | en |
dc.contributor.author | Papadopoulos, George K. | en |
dc.contributor.author | Archontis, Georgios Z. | en |
dc.contributor.author | Huizinga, T. W. | en |
dc.contributor.author | Toes, R. E. | en |
dc.creator | Van Heemst, J. | en |
dc.creator | Jansen, D. T. S. L. | en |
dc.creator | Polydorides, Savvas | en |
dc.creator | Moustakas, Antonis K. | en |
dc.creator | Bax, M. | en |
dc.creator | Feitsma, A. L. | en |
dc.creator | Bontrop-Elferink, D. G. | en |
dc.creator | Baarse, M. | en |
dc.creator | Van Der Woude, D. | en |
dc.creator | Wolbink, G. -J | en |
dc.creator | Rispens, T. | en |
dc.creator | Koning, F. | en |
dc.creator | De Vries, R. R. P. | en |
dc.creator | Papadopoulos, George K. | en |
dc.creator | Archontis, Georgios Z. | en |
dc.creator | Huizinga, T. W. | en |
dc.creator | Toes, R. E. | en |
dc.date.accessioned | 2019-12-02T15:34:42Z | |
dc.date.available | 2019-12-02T15:34:42Z | |
dc.date.issued | 2015 | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | http://gnosis.library.ucy.ac.cy/handle/7/59200 | |
dc.description.abstract | The HLA locus is the strongest risk factor for anti-citrullinated protein antibody (ACPA) + rheumatoid arthritis (RA). Despite considerable efforts in the last 35 years, this association is poorly understood. Here we identify (citrullinated) vinculin, present in the joints of ACPA + RA patients, as an autoantigen targeted by ACPA and CD4 + T cells. These T cells recognize an epitope with the core sequence DERAA, which is also found in many microbes and in protective HLA-DRB1∗13 molecules, presented by predisposing HLA-DQ molecules. Moreover, these T cells crossreact with vinculin-derived and microbial-derived DERAA epitopes. Intriguingly, DERAA-directed T cells are not detected in HLA-DRB1∗13 + donors, indicating that the DERAA epitope from HLA-DRB1∗13 mediates (thymic) tolerance in these donors and explaining the protective effects associated with HLA-DRB1∗13. Together our data indicate the involvement of pathogen-induced DERAA-directed T cells in the HLA-RA association and provide a molecular basis for the contribution of protective/predisposing HLA alleles. | en |
dc.source | Nature Communications | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84929224878&doi=10.1038%2fncomms7681&partnerID=40&md5=fe7c174ad21a96a87dc1bd1728919d10 | |
dc.subject | human | en |
dc.subject | Humans | en |
dc.subject | gamma interferon | en |
dc.subject | Interferon-gamma | en |
dc.subject | amino acid sequence | en |
dc.subject | biological model | en |
dc.subject | unclassified drug | en |
dc.subject | risk factor | en |
dc.subject | nonhuman | en |
dc.subject | T lymphocyte | en |
dc.subject | Article | en |
dc.subject | rheumatoid arthritis | en |
dc.subject | Autoantigens | en |
dc.subject | metabolism | en |
dc.subject | molecular genetics | en |
dc.subject | protein | en |
dc.subject | disease predisposition | en |
dc.subject | antibody | en |
dc.subject | human cell | en |
dc.subject | CD4+ T lymphocyte | en |
dc.subject | immunology | en |
dc.subject | antigen presentation | en |
dc.subject | Bacteria | en |
dc.subject | T-Lymphocytes | en |
dc.subject | Molecular Sequence Data | en |
dc.subject | donor | en |
dc.subject | chemistry | en |
dc.subject | HLA DR antigen | en |
dc.subject | molecular mechanics | en |
dc.subject | Tissue Donors | en |
dc.subject | Viruses | en |
dc.subject | chemical structure | en |
dc.subject | molecular dynamics | en |
dc.subject | Western blotting | en |
dc.subject | vinculin | en |
dc.subject | peripheral blood mononuclear cell | en |
dc.subject | bacterium | en |
dc.subject | Blotting, Western | en |
dc.subject | autoantigen | en |
dc.subject | antigen presenting cell | en |
dc.subject | epitope | en |
dc.subject | microbial activity | en |
dc.subject | pathogen | en |
dc.subject | molecular analysis | en |
dc.subject | virus | en |
dc.subject | Models, Molecular | en |
dc.subject | HLA antigen | en |
dc.subject | HLA DQ8 antigen | en |
dc.subject | antigen | en |
dc.subject | antigen recognition | en |
dc.subject | Arthritis, Rheumatoid | en |
dc.subject | citrulline | en |
dc.subject | cross reaction | en |
dc.subject | Cross Reactions | en |
dc.subject | disability | en |
dc.subject | enzyme linked immunospot assay | en |
dc.subject | Enzyme-Linked Immunospot Assay | en |
dc.subject | Epitopes | en |
dc.subject | HLA Antigens | en |
dc.subject | HLA DQ antigen | en |
dc.subject | HLA DQ5 antigen | en |
dc.subject | HLA DQ7 antigen | en |
dc.subject | HLA DQA1 antigen | en |
dc.subject | HLA DQB1 antigen | en |
dc.subject | HLA DRB1 antigen | en |
dc.subject | HLA SE antigen | en |
dc.subject | HLA system | en |
dc.subject | HLA-DQ Antigens | en |
dc.subject | HLA-DRB1 Chains | en |
dc.subject | microorganism | en |
dc.subject | Models, Immunological | en |
dc.subject | molecular mimicry | en |
dc.title | Crossreactivity to vinculin and microbes provides a molecular basis for HLA-based protection against rheumatoid arthritis | en |
dc.type | info:eu-repo/semantics/article | |
dc.identifier.doi | 10.1038/ncomms7681 | |
dc.description.volume | 6 | |
dc.author.faculty | Σχολή Θετικών και Εφαρμοσμένων Επιστημών / Faculty of Pure and Applied Sciences | |
dc.author.department | Τμήμα Φυσικής / Department of Physics | |
dc.type.uhtype | Article | en |
dc.description.notes | <p>Cited By :21</p> | en |
dc.source.abbreviation | Nat.Commun. | en |
dc.contributor.orcid | Archontis, Georgios Z. [0000-0002-7750-8641] | |
dc.gnosis.orcid | 0000-0002-7750-8641 |
Files in this item
Files | Size | Format | View |
---|---|---|---|
There are no files associated with this item. |