Unique glandular ex-vivo Th1 and Th17 receptor motifs in Sjögren's syndrome patients using single-cell analysis

Clin Immunol. 2018 Jul:192:58-67. doi: 10.1016/j.clim.2018.04.009. Epub 2018 Apr 19.

Abstract

Primary Sjögren's syndrome (pSS) is an autoimmune disease in which the underlying cause has yet to be elucidated. The main objective of this study was to determine the T cell receptor (TCR) repertoires of individual infiltrating T helper (Th)-1 and 17 cells of pSS patients using single-cell analysis. Single-cell analysis of ex-vivo infiltrating T cells demonstrated that pSS patients had higher frequencies of activated Th17 cells. Single-cell TCR sequencing revealed that TCRβ variable (TRBV)3-1/joint (J)1-2 (CLFLSMSACVW) and TRBV20-1/J1-1 (SVGSTAIPP*T) were expressed by activated Th1 and Th17 cells in both cohorts. Uniquely, TCRα variable (TRAV)8-2/J5 (VVSDTVLETAGE) was expressed by Th1 cells present only in patients and complementarity-determining region (CDR)3α-specific motif (LSTD*E) present in both Th1/Th17 cells. The study demonstrates that both activated Th1 and Th17 cells of pSS patients showed restricted clonal diversities of which two CDR3 motifs were present in controls and patients, with another two motifs unique to pSS.

Keywords: IFN-γ; IL-17A; Single-cell analysis; Sjögren's syndrome; T cell receptor; Th1; Th17.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Amino Acid Motifs / genetics
  • Amino Acid Motifs / immunology
  • Amino Acid Sequence
  • Cohort Studies
  • Female
  • Humans
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • Single-Cell Analysis / methods*
  • Sjogren's Syndrome / genetics
  • Sjogren's Syndrome / immunology*
  • Sjogren's Syndrome / metabolism
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Th17 Cells / immunology*
  • Th17 Cells / metabolism

Substances

  • Receptors, Antigen, T-Cell