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

Abstract

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. 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. 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. 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.