{"entity": "publication", "iuid": "1938da5a9fb54644b9fd03953d33a22d", "timestamp": "2026-08-09T14:05:28.333Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1938da5a9fb54644b9fd03953d33a22d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1938da5a9fb54644b9fd03953d33a22d"}}, "title": "Autoreactive T cells identified in patients with anti-Jo1+ antisynthetase syndrome recognise a new epitope on histidyl t-RNA synthetase.", "authors": [{"family": "Galindo-Feria", "given": "Angeles S", "initials": "AS"}, {"family": "Sharma", "given": "Ravi Kumar", "initials": "RK"}, {"family": "Dubnovitsky", "given": "Anatoly", "initials": "A"}, {"family": "Gerstner", "given": "Christina", "initials": "C"}, {"family": "Kozhukh", "given": "Genadiy", "initials": "G"}, {"family": "Van Vollenhoven", "given": "Annika", "initials": "A"}, {"family": "Boada", "given": "Juan Sebastian Diaz", "initials": "JSD"}, {"family": "Ramsk\u00f6ld", "given": "Daniel", "initials": "D", "orcid": "0000-0003-2892-673X", "researcher": {"href": "https://publications.scilifelab.se/researcher/cc367f2adb7c4379b7dc441be34e7ded.json"}}, {"family": "Achour", "given": "Adnane", "initials": "A"}, {"family": "Dastmalchi", "given": "Maryam", "initials": "M"}, {"family": "Reid", "given": "Hugh H", "initials": "HH"}, {"family": "Sandalova", "given": "Tatyana", "initials": "T"}, {"family": "Rossjohn", "given": "Jamie", "initials": "J"}, {"family": "Chemin", "given": "Karine", "initials": "K"}, {"family": "Malmstr\u00f6m", "given": "Vivianne", "initials": "V", "orcid": "0000-0001-9251-8082", "researcher": {"href": "https://publications.scilifelab.se/researcher/34027fbf97444632a470b33e446d4d67.json"}}, {"family": "Lundberg", "given": "Ingrid E", "initials": "IE", "orcid": "0000-0002-6068-9212", "researcher": {"href": "https://publications.scilifelab.se/researcher/40f6c8e761a944b78e67f0e04453f78b.json"}}, {"family": "Horuluoglu", "given": "Begum", "initials": "B", "orcid": "0000-0003-2241-5170", "researcher": {"href": "https://publications.scilifelab.se/researcher/19120340af6c42bd8a359ce39d4a8b99.json"}}], "type": "journal article", "published": "2025-10-25", "journal": {"title": "Ann. Rheum. Dis.", "issn": "1468-2060", "issn-l": "0003-4967"}, "abstract": "Anti-Jo1+ antisynthetase syndrome (ASyS) is characterised by autoantibodies targeting histidyl t-RNA synthetase (HisRS), association with HLA-DRB1*03:01 and a distinct clinical phenotype including interstitial lung disease, myositis, arthritis, and mechanic's hands. Previous studies of autoreactive HisRS-specific CD4+T cells point to yet undiscovered T cell epitopes. We aimed to identify new epitopes on HisRS to investigate the presence of autoreactive T cells and their corresponding T-cell receptor (TCR) repertoire from patients with ASyS.\n\nPeptides from HisRS N-terminal region with appropriate major histocompatibility complex (MHC) anchor residues were selected for in vitro binding assays. The peptide (HisRS41-55) with the highest HLA-DRB1*03:01 binding affinity was selected for studies with HLA-class II tetramers. Peripheral blood mononuclear cells (PBMCs) from patients with ASyS with HLA-DRB1*03:01 (n = 12) were stimulated in vitro with peptide and peptide-HLA-DRB1*03:01 tetramers were used to detect HisRS+CD4+T cells. Single TCR sequencing of captured T cells allowed analyses of the underlying TCR repertoire.\n\nWe identified a new T cell epitope on HisRS with high affinity for HLA-DRB1*03:01. Autoreactive HisRS+CD4+T cells were detected in PBMCs of patients (n = 6/12). TCR repertoire analysis of HisRS+CD4+T cells revealed shared gene V-alpha and beta usages. Moreover, HisRS+CD4+T cells persisted after treatment in 2 patients (P2 and P4) and 2 identical T cell clones were detected between the initial and follow-up time points in 1 patient (P2).\n\nAutoreactive T-cells targeting a new HisRS epitope were identified indicating T cell reactivity to diverse epitopes of the HisRS protein in patients with anti-Jo1 autoantibodies. Furthermore, we demonstrated the TCR repertoire of autoreactive HisRS+CD4+T cells in patients. Persistence of these T-cells and specific clones may be contributing to disease.", "doi": "10.1016/j.ard.2025.09.015", "pmid": "41139557", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Single cell": "Service", "NGI Short read": "Service"}, "xrefs": [{"db": "pii", "key": "S0003-4967(25)04429-2"}], "notes": [], "created": "2025-10-29T10:08:57.216Z", "modified": "2025-11-11T13:53:36.238Z"}