Characteristics of the (Auto)Reactive T Cells in Rheumatoid Arthritis According to the Immune Epitope Database

Abstract

T cells are known to be involved in the pathogenesis of rheumatoid arthritis (RA). Accordingly, and to better understand T cells’ contribution to RA, a comprehensive review based on an analysis of the Immune Epitope Database (IEDB) was conducted. An immune CD8+ T cell senescence response is reported in RA and inflammatory diseases, which is driven by active viral antigens from latent viruses and cryptic self-apoptotic peptides. RA-associated pro-inflammatory CD4+ T cells are selected by MHC class II and immunodominant peptides, which are derived from molecular chaperones, host extra-cellular and cellular peptides that could be post-translationally modified (PTM), and bacterial cross-reactive peptides. A large panel of techniques have been used to characterize (auto)reactive T cells and RA-associated peptides with regards to their interaction with the MHC and TCR, capacity to enter the docking site of the shared epitope (DRB1-SE), capacity to induce T cell proliferation, capacity to select T cell subsets (Th1/Th17, Treg), and clinical contribution. Among docking DRB1-SE peptides, those with PTM expand autoreactive and high-affinity CD4+ memory T cells in RA patients with an active disease. Considering original therapeutic options in RA, mutated, or altered peptide ligands (APL) have been developed and are tested in clinical trials.

Integrated analysis of single-cell RNA-seq, bulk RNA-seq, Mendelian randomization, and eQTL reveals T cell-related nomogram model and subtype classification in rheumatoid arthritis

“…A variety of cytokines released by different T cell subsets are involved in the inflammatory microenvironment of RA ( 21 ).For example, Th17 cells can promote macrophages, synoviocytes and other cells to secrete a large number of inflammatory factors such as IL-1β and IL-6 by producing IL-17 and also contribute to the production of CXCL1, CXCL2, CXCL8 and other chemokines ( 4 , 22 ). Overactivation of T cells is a factor that triggers maintains RA ( 1 ). Therefore, understanding the molecular mechanisms associated with T cells from multiple aspects will help to discover more immunotherapy methods for RA.…”

“…Rheumatoid arthritis (RA) is a commonly occurring autoimmune disease that affects 0.5–1% of the world’s population ( 1 ). The mechanism of RA has not yet been elucidated, and an effective cure is still lacking.…”

Predictive risk factors before the onset of familial rheumatoid arthritis: the Tatarstan cohort study

“…The HLA-DRB1 SE overrepresentation in RA was historically defined through the demonstration that the presence of HLA-DRB1 risk alleles harboring SE leads to the non-proliferative state in co-cultured lymphocytes from RA patients, which was not the case when using lymphocytes from healthy subjects ( 25 – 28 ). Next, it was reported that HLA-DRB1 SE represented the most predominant genetic risk factor associated with RA ( 29 ), and this overrepresentation was observed in 55% of the FDR from RA patients as compared to 43% in the HC group from North America ( 30 ).…”