TCR repertoire and CDR3 motif analyses depict the role of αβ T cells in Ankylosing spondylitis

EBioMedicine. 2019 Sep;47:414-426. doi: 10.1016/j.ebiom.2019.07.032. Epub 2019 Aug 30.

Abstract

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease with worldwide high prevalence. Although AS is strongly associated with HLA-B27 MHC-I antigen presentation, the role played by αβ T cells in AS remains elusive.

Methods: Utilizing TCRβ repertoire sequencing and bioinformatics tools developed in house, we analyzed overall TCR repertoire structures and antigen-recognizing CDR3 motifs in AS patients with different disease activities.

Findings: We found that disease progression is associated with both CD4+ and CD8+ T cell oligo-clonal expansion, which suggests that αβ T cell activation may mediate AS disease progression. By developing a bioinformatics platform to dissect antigen-specific responses, we discovered a cell population consisting of both CD4+ and CD8+ T cells expressing identical TCRs, herein termed CD4/8 T cells. CD4/8 clonotypes were highly enriched in the spondyloarthritic joint fluid of patients, and their expansion correlated with the activity of disease.

Interpretation: These results provide evidence on the T cell clone side to reveal the potential role of CD4/8 T cells in the etiology of AS development.

Keywords: Ankylosing spondylitis; Autoimmune disease; Complementarity determining region 3; Human; T cells; TCR repertoire.

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Autoimmune Diseases / etiology
  • Autoimmune Diseases / metabolism
  • Biomarkers
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Complementarity Determining Regions / chemistry
  • Complementarity Determining Regions / metabolism*
  • Disease Susceptibility
  • Humans
  • Immunohistochemistry
  • Receptors, Antigen, T-Cell / metabolism*
  • Spondylitis, Ankylosing / etiology*
  • Spondylitis, Ankylosing / metabolism*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*
  • Young Adult

Substances

  • Biomarkers
  • Complementarity Determining Regions
  • Receptors, Antigen, T-Cell