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Review
. 2023 Feb 21;24(5):4296.
doi: 10.3390/ijms24054296.

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

Caroline Carlé  1   2   3 , Yannick Degboe  3   4 , Adeline Ruyssen-Witrand  4 , Marina I Arleevskaya  5   6 , Cyril Clavel  2   3 , Yves Renaudineau  1   3
Affiliations
Review

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

Caroline Carlé et al. Int J Mol Sci. .

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.

Keywords: memory T cells; neoepitopes; peptides; rheumatoid arthritis; shared epitope.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Persistent/chronic infections favor the expansion of immunosenescent (is)CD8+ T cells in patients with rheumatoid arthritis.
Figure 2
Figure 2
Venn diagram of antigens (A) and epitopes (B) reported in patients with rheumatoid arthritis (RA) from the Immune Epitope Database (https://www.IEDB.org, accessed on 7 February 2023) that reports T cells, B cells, and major histocompatibility (MHC) assays.
Figure 3
Figure 3
Several antigens, including heat shock proteins (HSP) 60, collagen 2 (Col2), and human cartilage glycoprotein (gp)39, are immunogenic and associated with disease onset. Altered peptide ligands from these antigens are effective to shift the pro-inflammatory (TH1/TH17) cellular immune response into an anti-inflammatory (TH2) and or regulatory (Treg) T cell response.
See this image and copyright information in PMC

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