{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T17:15:42Z","timestamp":1787764542894,"version":"build-2784847793"},"reference-count":51,"publisher":"American Society for Clinical Investigation","issue":"17","license":[{"start":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T00:00:00Z","timestamp":1725321600000},"content-version":"vor","delay-in-days":61,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"crossref","award":["MO 2160\/4-1"],"award-info":[{"award-number":["MO 2160\/4-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"crossref","award":["Advanced Clinician Scientist-Program INTERACT"],"award-info":[{"award-number":["Advanced Clinician Scientist-Program INTERACT"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"crossref","award":["01EO2108"],"award-info":[{"award-number":["01EO2108"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009139","name":"German Center for Infection Research","doi-asserted-by":"crossref","award":["Clinical Leave Program"],"award-info":[{"award-number":["Clinical Leave Program"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009139","name":"German Center for Infection Research","doi-asserted-by":"crossref","award":["TI07.001_007"],"award-info":[{"award-number":["TI07.001_007"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Interdisciplinary Center for Clinical Research (IZKF) W\u00fcrzburg","award":["Clinician Scientist Program,Z-2\/CSP-30"],"award-info":[{"award-number":["Clinician Scientist Program,Z-2\/CSP-30"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,3]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>\n                      Antibiotic-Refractory Lyme Arthritis (ARLA) involves a complex interplay of T cell responses targeting\n                      <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                      antigens progressing toward autoantigens by epitope spreading. However, the precise molecular mechanisms driving the pathogenic T cell response in ARLA remain unclear. Our aim was to elucidate the molecular program of disease-specific Th cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Using flow cytometry, high-throughput T cell receptor (TCR) sequencing, and scRNA-Seq of CD4\n                      <jats:sup>+<\/jats:sup>\n                      Th cells isolated from the joints of patients with ARLA living in Europe, we aimed to infer antigen specificity through unbiased analysis of TCR repertoire patterns, identifying surrogate markers for disease-specific TCRs, and connecting TCR specificity to transcriptional patterns.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      PD-1\n                      <jats:sup>hi<\/jats:sup>\n                      HLA-DR\n                      <jats:sup>+<\/jats:sup>\n                      CD4\n                      <jats:sup>+<\/jats:sup>\n                      effector T cells were clonally expanded within the inflamed joints and persisted throughout disease course. Among these cells, we identified a distinct TCR-\u03b2 motif restricted to HLA-DRB1*11 or *13 alleles. These alleles, being underrepresented in patients with ARLA living in North America, were unexpectedly prevalent in our European cohort. The identified TCR-\u03b2 motif served as surrogate marker for a convergent TCR response specific to ARLA, distinguishing it from other rheumatic diseases. In the scRNA-Seq data set, the TCR-\u03b2 motif particularly mapped to peripheral T helper (T\n                      <jats:sub>PH<\/jats:sub>\n                      ) cells displaying signs of sustained proliferation, continuous TCR signaling, and expressing CXCL13 and IFN-\u03b3.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      By inferring disease-specific TCRs from synovial T cells we identified a convergent TCR response in the joints of patients with ARLA that continuously fueled the expansion of T\n                      <jats:sub>PH<\/jats:sub>\n                      cells expressing a pathogenic cytokine effector program. The identified TCRs will aid in uncovering the major antigen targets of the maladaptive immune response.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>Supported by the German Research Foundation (DFG) MO 2160\/4-1; the Federal Ministry of Education and Research (BMBF; Advanced Clinician Scientist-Program INTERACT; 01EO2108) embedded in the Interdisciplinary Center for Clinical Research (IZKF) of the University Hospital W\u00fcrzburg; the German Center for Infection Research (DZIF; Clinical Leave Program; TI07.001_007) and the Interdisciplinary Center for Clinical Research (IZKF) W\u00fcrzburg (Clinician Scientist Program, Z-2\/CSP-30).<\/jats:p>\n                  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