title: Single-cell analysis of glandular T cell receptors in Sjögren's syndrome.
abstract: CD4+T cells predominate in salivary gland (SG) inflammatory lesions in Sjögren's syndrome (SS). However, their antigen specificity, degree of clonal expansion, and relationship to clinical disease features remain unknown. We used multiplex reverse-transcriptase PCR to amplify paired T cell receptor α (TCRα) and β transcripts of single CD4+CD45RA-T cells from SG and peripheral blood (PB) of 10 individuals with primary SS, 9 of whom shared the HLA DR3/DQ2 risk haplotype. TCRα and β sequences were obtained from a median of 91 SG and 107 PB cells per subject. The degree of clonal expansion and frequency of cells expressing two productively rearranged α genes were increased in SG versus PB. Expanded clones from SG exhibited complementary-determining region 3 (CDR3) sequence similarity both within and among subjects, suggesting antigenic selection and shared antigen recognition. CDR3 similarities were shared among expanded clones from individuals discordant for canonical Ro and La autoantibodies, suggesting recognition of alternative SG antigen(s). The extent of SG clonal expansion correlated with reduced saliva production and increased SG fibrosis, linking expanded SG T cells with glandular dysfunction. Knowledge of paired TCRα and β sequences enables further work toward identification of target antigens and development of novel therapies.
authors.affiliation: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Joachims
authors.affiliation: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA; Department of Pathology, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, Oklahoma, USA.
authors.forename: Kerry M
authors.initials: KM
authors.lastname: Leehan
authors.affiliation: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Lawrence
authors.affiliation: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Pelikan
authors.affiliation: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA.
authors.forename: Jacen S
authors.initials: JS
authors.lastname: Moore
authors.affiliation: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA.
authors.forename: Zijian
authors.initials: Z
authors.lastname: Pan
authors.affiliation: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA.
authors.forename: Astrid
authors.initials: A
authors.lastname: Rasmussen
authors.affiliation: Department of Oral Diagnosis and Radiology, College of Dentistry, OUHSC, Oklahoma City, Oklahoma, USA.
authors.forename: Lida
authors.initials: L
authors.lastname: Radfar
authors.affiliation: Department of Oral and Maxillofacial Pathology, College of Dentistry, OUHSC, Oklahoma City, Oklahoma, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Lewis
authors.affiliation: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA.
authors.forename: Kiely M
authors.initials: KM
authors.lastname: Grundahl
authors.affiliation: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Kelly
authors.affiliation: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA.
authors.forename: Graham B
authors.initials: GB
authors.lastname: Wiley
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia; Pirogov Russian National Research Medical University, Moscow, Russia; Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Shugay
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia; Pirogov Russian National Research Medical University, Moscow, Russia; Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Dmitriy M
authors.initials: DM
authors.lastname: Chudakov
authors.affiliation: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA; Department of Pathology, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, Oklahoma, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lessard
authors.affiliation: Department of Ophthalmology, College of Medicine, OUHSC, Oklahoma City, Oklahoma, USA.
authors.forename: Donald U
authors.initials: DU
authors.lastname: Stone
authors.affiliation: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA; Department of Pathology, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, Oklahoma, USA; Section of Endocrinology and Diabetes, College of Medicine, OUHSC, Oklahoma City, Oklahoma, USA.
authors.forename: R Hal
authors.initials: RH
authors.lastname: Scofield
authors.affiliation: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA.
authors.forename: Courtney G
authors.initials: CG
authors.lastname: Montgomery
authors.affiliation: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA; Department of Pathology, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, Oklahoma, USA.
authors.forename: Kathy L
authors.initials: KL
authors.lastname: Sivils
authors.affiliation: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA.
authors.forename: Linda F
authors.initials: LF
authors.lastname: Thompson
authors.affiliation: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA; Department of Pathology, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, Oklahoma, USA.
authors.forename: A Darise
authors.initials: AD
authors.lastname: Farris