Publication details

Single-cell analysis of glandular T cell receptors in Sjögren's syndrome

Authors	JOACHIMS Michelle L. LEEHAN Kerry M. LAWRENCE Christina PELIKAN Richard C. MOORE Jacen S. PAN Zijian RASMUSSEN Astrid RADFAR Lida LEWIS David M. GRUNDAHL Kiely M. KELLY Jennifer A. WILEY Graham B. SHUGAY Mikhail CHUDAKOV Dmitriy LESSARD Christopher J. STONE Donald U. SCOFIELD R. Hal MONTGOMERY Courtney G. SIVILS Kathy L. THOMPSON Linda F. FARRIS A. Darise
Year of publication	2016
Type	Article in Periodical
Magazine / Source	JCI Insight
MU Faculty or unit	Central European Institute of Technology
Citation
Web	https://insight.jci.org/articles/view/85609/pdf
Doi	http://dx.doi.org/10.1172/jci.insight.85609
Field	Oncology and hematology
Keywords	Sjögren's syndrome; receptors; glandular; CD4; T cells
Description	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 alfa (TCR alfa) and beta 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. TCR alfa and beta 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 alfa 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 TCR alfa and beta sequences enables further work toward identification of target antigens and development of novel therapies.