Ding Yan, Huang Ling, Wu Yandan, Yan Jialai
Department of Clinical Laboratory, the Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China 210003.
Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu, China 210009.
Virus Res. 2025 Jun 23;358:199602. doi: 10.1016/j.virusres.2025.199602.
Human immunodeficiency virus (HIV) persists as a formidable and far - reaching threat without a cure. T cells are crucial for antiviral immunity and pathology in HIV patients, with specific T cell epitopes potentially key to effective therapies and HIV cure methods.
Identifying sufficient T-cell epitopes within the HIV proteome holds great significance. It can not only substantially accelerate the development of T-cell epitope-based vaccines but also enable a highly precise evaluation of the host's HIV-specific cellular immunity. This research provides an overview of functionally verified T-cell epitopes derived from HIV antigens, the human leukocyte antigen (HLA) alleles, as well as the screening and identification strategies.
Totally, 239 and 82 epitopes have been verified for CD8 T-cell and CD4 T-cell respectively by functional experiments. The majority are presented by various HLA supertypes, such as HLA-B35, B5301, A6802 or A0201, and DRB1 molecules. Furthermore, 74 % of the epitopes for CD8T-cell belong to Gag, Pol, as well as Nef Protein while 68 % of the CD4 T-cell epitopes originate from Gag protein. Antigenic peptides of HIV-1 subtypes A/B/C/D/CRF01_AE account for 11.43 %, 58.26 %, 21.69 %, 4.96 %, and 3.65 %, respectively.
The 321 T-cell epitope repertoires of HIV encompass the HLA polymorphisms of the main populations and subtypes in a particular geographical area. These epitope catalogs provide strong support for researching therapeutic vaccines, specific T-cell detection, and the interaction mechanism between HIV and the immune system. However, the limitations of the identified T-cell epitope library, the polymorphism of HLA molecules, and the high mutation rate of HIV require more research to cover the entire HIV proteome and the comprehensive landscape of T-cell epitopes in global patients.
人类免疫缺陷病毒（HIV）仍然是一个难以克服且影响深远的威胁，目前尚无治愈方法。T细胞对于HIV患者的抗病毒免疫和病理过程至关重要，特定的T细胞表位可能是有效治疗和治愈HIV方法的关键。
在HIV蛋白质组中鉴定出足够的T细胞表位具有重要意义。这不仅可以大幅加速基于T细胞表位的疫苗研发，还能对宿主的HIV特异性细胞免疫进行高度精确的评估。本研究概述了源自HIV抗原、人类白细胞抗原（HLA）等位基因的功能验证T细胞表位，以及筛选和鉴定策略。
通过功能实验分别验证了239个CD8 T细胞表位和82个CD4 T细胞表位。大多数表位由各种HLA超型呈递，如HLA-B35、B5301、A6802或A0201以及DRB1分子。此外，CD8 T细胞表位的74%属于Gag、Pol以及Nef蛋白，而68%的CD4 T细胞表位源自Gag蛋白。HIV-1 A/B/C/D/CRF01_AE亚型的抗原肽分别占11.43%、58.26%、21.69%、4.96%和3.65%。
HIV的321个T细胞表位库涵盖了特定地理区域主要人群和亚型的HLA多态性。这些表位目录为研究治疗性疫苗、特定T细胞检测以及HIV与免疫系统之间的相互作用机制提供了有力支持。然而，已鉴定的T细胞表位库的局限性、HLA分子的多态性以及HIV的高突变率需要更多研究来覆盖整个HIV蛋白质组和全球患者T细胞表位的全面情况。
