Referral Medical Biology Laboratory, Immunology Department, Institut Fédératif de Biologie, Toulouse University Hospital Center, 31300 Toulouse, France.
Laboratory of Cell Biology and Cytology, Institut Fédératif de Biologie, Toulouse University Hospital Center, 31300 Toulouse, France.
Int J Mol Sci. 2023 Feb 21;24(5):4296. doi: 10.3390/ijms24054296.
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.
T 细胞被认为参与了类风湿关节炎（RA）的发病机制。因此，为了更好地了解 T 细胞对 RA 的贡献，我们基于免疫表位数据库（IEDB）进行了全面的综述分析。有研究报道，在 RA 和炎症性疾病中存在 CD8+T 细胞衰老反应，这是由潜伏病毒的活性病毒抗原和隐蔽的细胞凋亡肽驱动的。与 RA 相关的促炎 CD4+T 细胞是由 MHC Ⅱ类和免疫显性肽选择的，这些肽来源于分子伴侣、宿主细胞外和细胞肽，它们可能发生翻译后修饰（PTM）和细菌交叉反应肽。已经使用了大量技术来描述（自身）反应性 T 细胞和 RA 相关肽与 MHC 和 TCR 的相互作用、进入共享表位（DRB1-SE）结合位点的能力、诱导 T 细胞增殖的能力、选择 T 细胞亚群（Th1/Th17、Treg）的能力以及临床贡献。在结合 DRB1-SE 的肽中，那些具有 PTM 的肽可以在疾病活动期的 RA 患者中扩增自身反应性和高亲和力的 CD4+记忆 T 细胞。考虑到 RA 的原始治疗选择，已经开发并正在临床试验中测试突变或改变的肽配体（APL）。
