Antigen-specific immune reactions by expanded CD8+T cell clones from HLA-B*27-positive patients with spondyloarthritis

Spondyloarthritis (SpA) is a chronic inflammatory disease that is tightly linked to HLA-B*27 but the patho-physiological basis of this link is still unknown. It is discussed whether either the instability of HLA-B*27 molecules triggers predominantly innate immune reactions or yet unknown antigenic peptides presented by HLA-B*27 induce adaptive autoimmune reactions by CD8+ T cells. To analyze the pathogenesis of SpA, we here investigated the T cell receptor (TCR) usage and whole transcriptomes of CD8+ single cells from synovial fluid of HLA-B*27-positive SpA patients and HLA-B*27-negative controls. In HLA-B*27-positive patients, we confirmed preferential expression of several TCR beta-chain families, found even more restricted usage of particular TCR alpha-chains, assigned matching TCR alpha beta-chain pairs with homologous CDR3-sequences, and detected identical TCR-chains in different patients. Gene expression analyses by single cell mRNAseq revealed that genes specific for the tissue resident memory phenotype, exhaustion, and apoptosis were particularly highly expressed in expanded clonotypes from HLA-B*27-positive SpA patients. Together, several independent lines of evidence argue in favor of an (auto)antigenic peptide related pathogenesis.

Automated summary

This study investigated the T cell receptor (TCR) usage and whole transcriptomes of CD8+ single cells to analyze the pathogenesis of Spondyloarthritis (SpA). The findings suggest that (auto)antigenic peptides may play a role in the development of SpA.