Hantaan virus-derived peptides that stabilize HLA-E could abrogate inhibition of CD56dimNKG2A+ NK cells.
NK cells could participate in the pathogenesis process of virus infectious diseases through the inhibitory receptor CD94/NKG2A interacting with HLA-E/virus-derived peptide complex. However, the effects and mechanisms of NKG2A-HLA-E axis-mediated NK cell responses in hemorrhagic fever with renal synd...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-07-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1012717 |
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| author | Manling Xue Kang Tang Yusi Zhang Xiaoyue Xu Chunmei Zhang Jiajia Zuo Fenglan Wang Xiyue Zhang Xuyang Zheng Ran Zhuang Yun Zhang Boquan Jin Ying Ma |
| author_facet | Manling Xue Kang Tang Yusi Zhang Xiaoyue Xu Chunmei Zhang Jiajia Zuo Fenglan Wang Xiyue Zhang Xuyang Zheng Ran Zhuang Yun Zhang Boquan Jin Ying Ma |
| author_sort | Manling Xue |
| collection | DOAJ |
| description | NK cells could participate in the pathogenesis process of virus infectious diseases through the inhibitory receptor CD94/NKG2A interacting with HLA-E/virus-derived peptide complex. However, the effects and mechanisms of NKG2A-HLA-E axis-mediated NK cell responses in hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus (HTNV) infection remain unclear. Single-cell RNA sequencing and flow cytometry were employed to analyze the phenotype and function of different NK cell subsets in HFRS patients. The K562/HLA-E cells binding assay was used for peptide affinity detection. The binding capacity of HLA-E/peptide-CD94/NKG2A was detected using ligand-receptor binding assay and tetramer staining. The cytotoxicity assay of NK cells against peptide-pulsed K562/HLA-E cells was conducted for functional evaluation. In this study, CD56dimCD16+NKG2A+ NK cells were the main subset in HFRS patients, showing activation and proliferation phenotypes with NKG2C-CD57- and the ability to secrete tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and cytotoxic mediators. Notably, none of the four identified HTNV epitopes presented by HLA-E could be recognized by CD94/NKG2A on CD56dimNKG2A+ NK cells. Furthermore, the subset of CD56dimNKG2A+ NK cells showed the enhanced cytolytic capacity against HTNV peptide pulsed K562/HLA-E cells ex vivo. Taken together, the findings demonstrate that HTNV-derived peptides presented by HLA-E could "abrogate" the inhibition of CD56dimNKG2A+ NK cells, contributing to the antiviral immune response in HFRS patients. |
| format | Article |
| id | doaj-art-eb3a549be11747558552ae80cc078efe |
| institution | DOAJ |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-eb3a549be11747558552ae80cc078efe2025-08-20T02:47:36ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-07-01217e101271710.1371/journal.ppat.1012717Hantaan virus-derived peptides that stabilize HLA-E could abrogate inhibition of CD56dimNKG2A+ NK cells.Manling XueKang TangYusi ZhangXiaoyue XuChunmei ZhangJiajia ZuoFenglan WangXiyue ZhangXuyang ZhengRan ZhuangYun ZhangBoquan JinYing MaNK cells could participate in the pathogenesis process of virus infectious diseases through the inhibitory receptor CD94/NKG2A interacting with HLA-E/virus-derived peptide complex. However, the effects and mechanisms of NKG2A-HLA-E axis-mediated NK cell responses in hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus (HTNV) infection remain unclear. Single-cell RNA sequencing and flow cytometry were employed to analyze the phenotype and function of different NK cell subsets in HFRS patients. The K562/HLA-E cells binding assay was used for peptide affinity detection. The binding capacity of HLA-E/peptide-CD94/NKG2A was detected using ligand-receptor binding assay and tetramer staining. The cytotoxicity assay of NK cells against peptide-pulsed K562/HLA-E cells was conducted for functional evaluation. In this study, CD56dimCD16+NKG2A+ NK cells were the main subset in HFRS patients, showing activation and proliferation phenotypes with NKG2C-CD57- and the ability to secrete tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and cytotoxic mediators. Notably, none of the four identified HTNV epitopes presented by HLA-E could be recognized by CD94/NKG2A on CD56dimNKG2A+ NK cells. Furthermore, the subset of CD56dimNKG2A+ NK cells showed the enhanced cytolytic capacity against HTNV peptide pulsed K562/HLA-E cells ex vivo. Taken together, the findings demonstrate that HTNV-derived peptides presented by HLA-E could "abrogate" the inhibition of CD56dimNKG2A+ NK cells, contributing to the antiviral immune response in HFRS patients.https://doi.org/10.1371/journal.ppat.1012717 |
| spellingShingle | Manling Xue Kang Tang Yusi Zhang Xiaoyue Xu Chunmei Zhang Jiajia Zuo Fenglan Wang Xiyue Zhang Xuyang Zheng Ran Zhuang Yun Zhang Boquan Jin Ying Ma Hantaan virus-derived peptides that stabilize HLA-E could abrogate inhibition of CD56dimNKG2A+ NK cells. PLoS Pathogens |
| title | Hantaan virus-derived peptides that stabilize HLA-E could abrogate inhibition of CD56dimNKG2A+ NK cells. |
| title_full | Hantaan virus-derived peptides that stabilize HLA-E could abrogate inhibition of CD56dimNKG2A+ NK cells. |
| title_fullStr | Hantaan virus-derived peptides that stabilize HLA-E could abrogate inhibition of CD56dimNKG2A+ NK cells. |
| title_full_unstemmed | Hantaan virus-derived peptides that stabilize HLA-E could abrogate inhibition of CD56dimNKG2A+ NK cells. |
| title_short | Hantaan virus-derived peptides that stabilize HLA-E could abrogate inhibition of CD56dimNKG2A+ NK cells. |
| title_sort | hantaan virus derived peptides that stabilize hla e could abrogate inhibition of cd56dimnkg2a nk cells |
| url | https://doi.org/10.1371/journal.ppat.1012717 |
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