Human MHC-II with Shared Epitope Motifs Are Optimal Epstein-Barr Virus Glycoprotein 42 Ligands—Relation to Rheumatoid Arthritis

Nicole Trier*, Jose Maria Gonzalez-Izarzugaza, Anna Chailyan, Paolo Marcatili, Gunnar Houen

*Corresponding author for this work

    Research output: Contribution to journalJournal articleResearchpeer-review

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    Abstract

    Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder of unknown etiology, which is characterized by inflammation in the synovium and joint damage. Although the pathogenesis of RA remains to be determined, a combination of environmental (e.g., viral infections) and genetic factors influence disease onset. Especially genetic factors play a vital role in the onset of disease, as the heritability of RA is 50–60%, with the human leukocyte antigen (HLA) alleles accounting for at least 30% of the overall genetic risk. Some HLA-DR alleles encode a conserved sequence of amino acids, referred to as the shared epitope (SE) structure. By analyzing the structure of a HLA-DR molecule in complex with Epstein-Barr virus (EBV), the SE motif is suggested to play a vital role in the interaction of MHC II with the viral glycoprotein (gp) 42, an essential entry factor for EBV. EBV has been repeatedly linked to RA by several lines of evidence and, based on several findings, we suggest that EBV is able to induce the onset of RA in predisposed SE-positive individuals, by promoting entry of B-cells through direct contact between SE and gp42 in the entry complex
    Original languageEnglish
    Article number317
    JournalInternational Journal of Molecular Sciences (Online)
    Volume19
    Issue number1
    Number of pages18
    ISSN1661-6596
    DOIs
    Publication statusPublished - 2018

    Bibliographical note

    This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

    Keywords

    • Epstein-Barr virus
    • Glycoprotein 42
    • Rheumatoid arthritis
    • Shared epitope

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