Differential expression profile of gluten-specific T cells identified by single-cell RNA-seq

PLoS One. 2021 Oct 7;16(10):e0258029. doi: 10.1371/journal.pone.0258029. eCollection 2021.


Gluten-specific CD4+ T cells drive the pathogenesis of celiac disease and circulating gluten-specific T cells can be identified by staining with HLA-DQ:gluten tetramers. In this first single-cell RNA-seq study of tetramer-sorted T cells from untreated celiac disease patients blood, we found that gluten-specific T cells showed distinct transcriptomic profiles consistent with activated effector memory T cells that shared features with Th1 and follicular helper T cells. Compared to non-specific cells, gluten-specific T cells showed differential expression of several genes involved in T-cell receptor signaling, translational processes, apoptosis, fatty acid transport, and redox potentials. Many of the gluten-specific T cells studied shared T-cell receptor with each other, indicating that circulating gluten-specific T cells belong to a limited number of clones. Moreover, the transcriptional profiles of cells that shared the same clonal origin were transcriptionally more similar compared with between clonally unrelated gluten-specific cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Celiac Disease / genetics*
  • Celiac Disease / pathology
  • Cell Lineage / genetics*
  • Gene Expression Profiling
  • Gene Expression Regulation / genetics*
  • Glutens / biosynthesis
  • Glutens / genetics*
  • Humans
  • RNA-Seq
  • Receptors, Antigen, T-Cell / genetics
  • Single-Cell Analysis
  • T-Lymphocytes / classification
  • T-Lymphocytes / metabolism*
  • Th1 Cells / metabolism
  • Th1 Cells / pathology


  • Receptors, Antigen, T-Cell
  • Glutens

Grant support

This work is funded by Research Council of Norway https://www.forskningsradet.no (project 179573/V40 through the Centre of Excellence funding scheme and project 233885), and grants from the Stiftelsen Kristian Gerhard Jebsen (SKGJ-MED-017). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.