{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:46:50Z","timestamp":1790790410109,"version":"4.1.0"},"posted":{"date-parts":[[2023,11,21]]},"group-title":"Immunology","reference-count":49,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,11,29]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>HLA-DR-expressing fibroblast-like synoviocytes (FLS) are a prominent cell type in synovial tissue in chronic inflammatory forms of arthritis. We recently showed that peptides from several extracellular matrix (ECM) proteins, including fibronectin-1 (FN1), contained immunogenic CD4+ T cell epitopes in patients with postinfectious Lyme arthritis (LA). However, the role of FLS in presentation of these T cell epitopes remains uncertain.<\/jats:p>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Primary LA FLS and primary murine FLS stimulated with interferon gamma (IFN\u03b3),\n                      <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                      , and\/or\n                      <jats:italic>B. burgdorferi<\/jats:italic>\n                      peptidoglycan (PG) were assessed for properties associated with antigen presentation. HLA-DR-presented peptides from stimulated LA FLS were identified by immunopeptidomics analysis. OT-II T cells were cocultured with stimulated murine FLS in the presence of cognate ovalbumin antigen to determine the potential of FLS to act as inducible antigen presenting cells (APC).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      FLS expressed HLA-DR molecules within inflamed synovial tissue and tendons from patients with post-infectious LA patients\n                      <jats:italic>in situ.<\/jats:italic>\n                      MHC class II and costimulatory molecules were expressed by FLS following\n                      <jats:italic>in vitro<\/jats:italic>\n                      stimulation with IFN\u03b3 and\n                      <jats:italic>B. burgdorferi<\/jats:italic>\n                      and presented both foreign and self MHC-II peptides, including T cell epitopes derived from two Lyme autoantigens fibronectin-1 (FN1) and endothelial cell growth factor (ECGF). Stimulated murine FLS induced proliferation of na\u00efve OT-II CD4+ T cells, particularly when FLS were stimulated with both IFN\u03b3 and PG.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>MHC-II+ FLS are inducible APCs that can induce CD4+ T cell activation and can present Lyme autoantigens derived from ECM proteins, thereby amplifying tissue-localized autoimmune CD4+ T cell responses in LA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>AUTHORS\u2019 SUMMARY<\/jats:title>\n                    <jats:p>\n                      This study demonstrates that IFN\u03b3-activated MHC-II+ fibroblast-like synoviocytes (FLS) stimulated with\n                      <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                      present foreign and self MHC-II antigens, including Lyme autoantigens. Furthermore, IFN\u03b3-activated MHC-II+ FLS stimulated with\n                      <jats:italic>B. burgdorferi<\/jats:italic>\n                      peptidoglycan can induce activation and proliferation of na\u00efve CD4+ T cells in an MHC-II antigen-dependent manner, demonstrating that activated MHC-II+ FLS are inducible antigen presenting cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                <\/jats:sec>","DOI":"10.1101\/2023.11.21.568066","type":"posted-content","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T20:11:20Z","timestamp":1700597480000},"source":"Crossref","is-referenced-by-count":2,"title":["Human leukocyte antigen HLA-DR-expressing fibroblast-like synoviocytes are inducible antigen presenting cells that present autoantigens in Lyme arthritis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8675-904X","authenticated-orcid":false,"given":"Joseph R","family":"Rouse","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2238-0916","authenticated-orcid":false,"given":"Rebecca","family":"Danner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Wahhab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7287-5450","authenticated-orcid":false,"given":"Michaela","family":"Pereckas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9071-540X","authenticated-orcid":false,"given":"Mecaila E","family":"McClune","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5268-9853","authenticated-orcid":false,"given":"Allen C","family":"Steere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0109-6791","authenticated-orcid":false,"given":"Klemen","family":"Strle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7989-1031","authenticated-orcid":false,"given":"Brandon L","family":"Jutras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7726-0466","authenticated-orcid":false,"given":"Robert B","family":"Lochhead","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2023120508000426000_2023.11.21.568066v2.1","doi-asserted-by":"crossref","unstructured":"Kanjana K , Strle K , Lochhead RB , Pianta A , Mateyka LM , Wang Q , et al. 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