Chen Ji-Li, Wang Beibei, Lu Yongxu, Antoun Elie, Bird Olivia, Drennan Philip G, Yin Zixi, Liu Guihai, Yao Xuan, Pidoux Maya, Bates Adam, Jayathilaka Deshni, Wang Junyuan, Angus Brian, Beer Sally, Espinosa Alexis, Baillie J Kenneth, Semple Malcolm G, Rostron Timothy, Waugh Craig, Sopp Paul, Knight Julian C, Fullerton James N, Coles Mark, Smith Geoffrey L, Mentzer Alexander J, Peng Yanchun, Dong Tao
Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
MRC Translational Immune Discovery Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Nat Commun. 2025 May 10;16(1):4362. doi: 10.1038/s41467-025-59370-5.
In 2022, a global mpox outbreak occurred, and remains a concern today. The T cell memory response to MPXV (monkeypox virus) infection has not been fully investigated. In this study, we evaluate this response in convalescent and MVA-BN (Modified Vaccinia Ankara - Bavarian Nordic) vaccinated individuals using VACV-infected cells. Strong CD8 and CD4 T cell responses are observed, and T cell responses are biased towards viral early expressed proteins. We identify seven immunodominant HLA-A02:01 restricted MPXV-specific epitopes and focus our detailed phenotypic and scRNAseq analysis on the immunodominant HLA-A02:01-G5R-specific CD8 T cell response. While tetramerCD8 T cells share similar differentiation and activation phenotypes, T cells from convalescent individuals show greater cytotoxicity, migratory potential to site of infection and TCR clonal expansion. Our data suggest that effective functional profiles of MPXV-specific memory T cells induced by Mpox infection may have an implication on the long-term protective responses to future infection.
2022年,全球发生了猴痘疫情,至今仍是人们关注的问题。针对猴痘病毒(MPXV)感染的T细胞记忆反应尚未得到充分研究。在本研究中,我们使用感染痘苗病毒(VACV)的细胞评估了康复者和接种MVA-BN(安卡拉改良痘苗病毒-巴伐利亚北欧公司)的个体的这种反应。观察到强烈的CD8和CD4 T细胞反应,并且T细胞反应偏向于病毒早期表达的蛋白。我们鉴定出七个免疫显性的HLA-A02:01限制性MPXV特异性表位,并将详细的表型和单细胞RNA测序分析集中在免疫显性的HLA-A02:01-G5R特异性CD8 T细胞反应上。虽然四聚体CD8 T细胞具有相似的分化和激活表型,但来自康复者的T细胞表现出更强的细胞毒性、向感染部位的迁移潜力和TCR克隆扩增。我们的数据表明,猴痘感染诱导的MPXV特异性记忆T细胞的有效功能特征可能对未来感染的长期保护反应有影响。