{"doi":"10.1172/jci.insight.188496","title":"Identification of Sjögren’s disease–associated T cell receptor motifs through deep sequencing","abstract":"CD4+ T cells predominate lymphocytic foci found in the salivary glands (SGs) of Sjögren's disease (SjD) cases. Yet little is known about T cell receptor (TCR) repertoire features that distinguish cases from healthy controls (HCs), the relationship between SG and peripheral blood (PB) repertoires of cases, and antigens recognized by pathogenic T cell clones. We performed deep sequencing of bulk-sorted CD4+CD45RA- PB T cells from SjD cases and matched HCs, and single-cell TCR sequencing of the same T cell population from labial SG biopsies of these cases. We found that clonally expanded SG CD4+ T cells expressed complementarity-determining region 3 (CDR3) sequences that were also detected in multiple copies in the blood of the same individuals with SjD. SjD cases displayed a \"private\" and restricted PB TCR repertoire with reduced clonotype diversity. We identified SjD-associated TCR motifs with the same putative antigen specificity shared between SGs and PB of cases. Their abundances in PB correlated with reduced salivary flow, linking these T cells with pathogenic disease features. Finally, we discovered 2 Ro60 epitopes eliciting an HLA-restricted immune response from expanded SG T cell clones. The comprehensive characterization of SjD TCR repertoires enables the discovery of target antigens and therapeutic strategies.","journal":"JCI Insight","year":2025,"id":529595,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9604,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1408437,"name":"Michelle L. Joachims","orcid":"0000-0001-7673-798X","position":1,"is_corresponding":false},{"id":494942,"name":"Christina Lawrence","orcid":null,"position":2,"is_corresponding":false},{"id":907982,"name":"Charmaine Lopez-Davis","orcid":"0000-0003-4219-6294","position":3,"is_corresponding":false},{"id":281374,"name":"Bhuwan Khatri","orcid":"0000-0001-5456-2963","position":4,"is_corresponding":false},{"id":380176,"name":"Astrid Rasmussen","orcid":"0000-0001-7744-2948","position":5,"is_corresponding":false},{"id":494945,"name":"Kiely Grundahl","orcid":null,"position":6,"is_corresponding":false},{"id":148454,"name":"R. Hal Scofield","orcid":null,"position":7,"is_corresponding":false},{"id":226234,"name":"Judith A. James","orcid":"0000-0002-9574-7355","position":8,"is_corresponding":false},{"id":226232,"name":"Joel M. Guthridge","orcid":"0000-0002-9308-237X","position":9,"is_corresponding":false},{"id":281380,"name":"Christopher J. Lessard","orcid":"0000-0003-2440-3843","position":10,"is_corresponding":false},{"id":494224,"name":"Linda F. Thompson","orcid":"0000-0002-0237-831X","position":11,"is_corresponding":false},{"id":419781,"name":"A. Darise Farris","orcid":"0000-0003-3009-2017","position":12,"is_corresponding":false},{"id":1030227,"name":"Ananth Aditya Jupudi","orcid":null,"position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-19T02:50:56.971987Z","pmid":"41424382","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}