Department of Immunology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran.
Biomed Pharmacother. 2024 Aug;177:116983. doi: 10.1016/j.biopha.2024.116983. Epub 2024 Jun 21.
The induction of immunological tolerance is a promising strategy for managing autoimmune diseases, allergies, and transplant rejection. Tregitopes, a class of peptides, have emerged as potential agents for this purpose. They activate regulatory T cells, which are pivotal in reducing inflammation and promoting tolerance, by binding to MHC II molecules and facilitating their processing and presentation to Treg cells, thereby encouraging their proliferation. Moreover, Tregitopes influence the phenotype of antigen-presenting cells by attenuating the expression of CD80, CD86, and MHC class II while enhancing ILT3, resulting in the inhibition of NF-kappa B signaling pathways. Various techniques, including in vitro and in silico methods, are applied to identify Tregitope candidates. Currently, Tregitopes play a vital role in balancing immune activation and tolerance in clinical applications such as Pompe disease, diabetes-related antigens, and the prevention of spontaneous abortions in autoimmune diseases. Similarly, Tregitopes can induce antigen-specific regulatory T cells. Their anti-inflammatory effects are significant in conditions such as autoimmune encephalomyelitis, inflammatory bowel disease, and Guillain-Barré syndrome. Additionally, Tregitopes have been leveraged to enhance vaccine design and efficacy. Recent advancements in understanding the potential benefits and drawbacks of IVIG and the discovery of the function and mechanism of Tregitopes have introduced Tregitopes as a popular option for immune system modulation. It is expected that they will bring about a significant revolution in the management and treatment of autoimmune and immunological diseases. This article is a comprehensive review of Tregitopes, concluding with the potential of these epitopes as a therapeutic avenue for immunological disorders.
免疫耐受的诱导是管理自身免疫性疾病、过敏和移植排斥的一种有前途的策略。Tregitopes 是一类肽，已成为该目的的潜在药物。它们通过与 MHC II 分子结合并促进其加工和呈递给 Treg 细胞，从而促进其增殖，来激活调节性 T 细胞，这些细胞在减少炎症和促进耐受方面起着关键作用。此外，Tregitopes 通过减弱 CD80、CD86 和 MHC 类 II 的表达，同时增强 ILT3，从而影响抗原呈递细胞的表型，抑制 NF-kappa B 信号通路。各种技术，包括体外和计算方法，都用于鉴定 Tregitope 候选物。目前，Tregitopes 在临床应用中（如庞贝病、糖尿病相关抗原和自身免疫性疾病中预防自然流产）平衡免疫激活和耐受方面发挥着重要作用。同样，Tregitopes 可以诱导抗原特异性调节性 T 细胞。它们的抗炎作用在自身免疫性脑脊髓炎、炎症性肠病和吉兰-巴雷综合征等疾病中非常显著。此外，Tregitopes 已被用于增强疫苗设计和功效。最近对 IVIG 的潜在益处和缺点的理解的进展以及 Tregitopes 的功能和机制的发现，将 Tregitopes 作为免疫系统调节的热门选择。预计它们将在自身免疫和免疫性疾病的管理和治疗方面带来重大变革。本文对 Tregitopes 进行了全面综述，结论是这些表位作为免疫性疾病治疗途径的潜力。
