HLA-A2 and B35 restricted hantaan virus nucleoprotein CD8+ T-cell epitope-specific immune response correlates with milder disease in hemorrhagic fever with renal syndrome.
BACKGROUND: Hantaan virus (HTNV) infection in humans is a serious public health concern in Asia. A potent T cell activation peptide vaccine from HTNV structure protein represents a promising immunotherapy for disease control. However, the T cell epitopes of the HTNV restricted by the HLA alleles and...
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ftdoajarticles:oai:doaj.org/article:18ee394ead074caa80b7580014a346c0 2023-05-15T15:15:43+02:00 HLA-A2 and B35 restricted hantaan virus nucleoprotein CD8+ T-cell epitope-specific immune response correlates with milder disease in hemorrhagic fever with renal syndrome. Ying Ma Jiuping Wang Bin Yuan Meiliang Wang Yun Zhang Zhuwei Xu Chunmei Zhang Yusi Zhang Bei Liu Jing Yi Kun Yang Angang Yang Ran Zhuang Boquan Jin 2013-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0002076 https://doaj.org/article/18ee394ead074caa80b7580014a346c0 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3585118?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002076 https://doaj.org/article/18ee394ead074caa80b7580014a346c0 PLoS Neglected Tropical Diseases, Vol 7, Iss 2, p e2076 (2013) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2013 ftdoajarticles https://doi.org/10.1371/journal.pntd.0002076 2022-12-30T23:24:28Z BACKGROUND: Hantaan virus (HTNV) infection in humans is a serious public health concern in Asia. A potent T cell activation peptide vaccine from HTNV structure protein represents a promising immunotherapy for disease control. However, the T cell epitopes of the HTNV restricted by the HLA alleles and the role of epitope-specific T cell response after HTNV infection remain largely unexplored. METHODOLOGY/PRINCIPAL FINDINGS: Five well-conserved novel CD8(+) T-cell epitopes of the HTNV nucleoprotein restricted by the most popular HLA alleles in Chinese Han population were defined with interferon-γ enzyme-linked immunospot assay in 37 patients infected with HTNV during hospitalization. Two epitopes aa129-aa137 and aa131-aa139 restricted by HLA-A2 and B35, respectively, were selected to evaluate the epitope-specific CD8(+) T-cell response. HLA-peptide pentamer complex staining showed that the frequency of single epitope-specific CD8(+) T cell could be detected in patients (95% confidence interval for aa129-aa137: 0.080%-0.208%; for aa131-aa139: 0.030%-0.094%). The frequency of epitope-specific pentamer(+) CD8(+) T-cell response was much higher in mild/moderate patients than in severe/critical ones at the acute stage of the disease. Moreover, the frequency of epitope-specific CD8(+) T cells at acute stage was inversely associated with the peak level of serum creatinine and was positively associated with the nadir platelet counts during the hospitalization. The intracellular cytokine staining and the proliferation assay showed that the effective epitope-specific CD8(+) T cells were characterized with the production of interferon-γ, expression of CD69 and the strong capacity of proliferation. CONCLUSION/SIGNIFICANCE: The novel HLA class I restricted HTNV nucleoprotein epitopes-specific CD8(+) T-cell responses would be closely related with the progression and the severity of the disease, which could provide the first step toward effective peptide vaccine development against HTNV infection in humans. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 7 2 e2076 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Ying Ma Jiuping Wang Bin Yuan Meiliang Wang Yun Zhang Zhuwei Xu Chunmei Zhang Yusi Zhang Bei Liu Jing Yi Kun Yang Angang Yang Ran Zhuang Boquan Jin HLA-A2 and B35 restricted hantaan virus nucleoprotein CD8+ T-cell epitope-specific immune response correlates with milder disease in hemorrhagic fever with renal syndrome. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND: Hantaan virus (HTNV) infection in humans is a serious public health concern in Asia. A potent T cell activation peptide vaccine from HTNV structure protein represents a promising immunotherapy for disease control. However, the T cell epitopes of the HTNV restricted by the HLA alleles and the role of epitope-specific T cell response after HTNV infection remain largely unexplored. METHODOLOGY/PRINCIPAL FINDINGS: Five well-conserved novel CD8(+) T-cell epitopes of the HTNV nucleoprotein restricted by the most popular HLA alleles in Chinese Han population were defined with interferon-γ enzyme-linked immunospot assay in 37 patients infected with HTNV during hospitalization. Two epitopes aa129-aa137 and aa131-aa139 restricted by HLA-A2 and B35, respectively, were selected to evaluate the epitope-specific CD8(+) T-cell response. HLA-peptide pentamer complex staining showed that the frequency of single epitope-specific CD8(+) T cell could be detected in patients (95% confidence interval for aa129-aa137: 0.080%-0.208%; for aa131-aa139: 0.030%-0.094%). The frequency of epitope-specific pentamer(+) CD8(+) T-cell response was much higher in mild/moderate patients than in severe/critical ones at the acute stage of the disease. Moreover, the frequency of epitope-specific CD8(+) T cells at acute stage was inversely associated with the peak level of serum creatinine and was positively associated with the nadir platelet counts during the hospitalization. The intracellular cytokine staining and the proliferation assay showed that the effective epitope-specific CD8(+) T cells were characterized with the production of interferon-γ, expression of CD69 and the strong capacity of proliferation. CONCLUSION/SIGNIFICANCE: The novel HLA class I restricted HTNV nucleoprotein epitopes-specific CD8(+) T-cell responses would be closely related with the progression and the severity of the disease, which could provide the first step toward effective peptide vaccine development against HTNV infection in humans. |
format |
Article in Journal/Newspaper |
author |
Ying Ma Jiuping Wang Bin Yuan Meiliang Wang Yun Zhang Zhuwei Xu Chunmei Zhang Yusi Zhang Bei Liu Jing Yi Kun Yang Angang Yang Ran Zhuang Boquan Jin |
author_facet |
Ying Ma Jiuping Wang Bin Yuan Meiliang Wang Yun Zhang Zhuwei Xu Chunmei Zhang Yusi Zhang Bei Liu Jing Yi Kun Yang Angang Yang Ran Zhuang Boquan Jin |
author_sort |
Ying Ma |
title |
HLA-A2 and B35 restricted hantaan virus nucleoprotein CD8+ T-cell epitope-specific immune response correlates with milder disease in hemorrhagic fever with renal syndrome. |
title_short |
HLA-A2 and B35 restricted hantaan virus nucleoprotein CD8+ T-cell epitope-specific immune response correlates with milder disease in hemorrhagic fever with renal syndrome. |
title_full |
HLA-A2 and B35 restricted hantaan virus nucleoprotein CD8+ T-cell epitope-specific immune response correlates with milder disease in hemorrhagic fever with renal syndrome. |
title_fullStr |
HLA-A2 and B35 restricted hantaan virus nucleoprotein CD8+ T-cell epitope-specific immune response correlates with milder disease in hemorrhagic fever with renal syndrome. |
title_full_unstemmed |
HLA-A2 and B35 restricted hantaan virus nucleoprotein CD8+ T-cell epitope-specific immune response correlates with milder disease in hemorrhagic fever with renal syndrome. |
title_sort |
hla-a2 and b35 restricted hantaan virus nucleoprotein cd8+ t-cell epitope-specific immune response correlates with milder disease in hemorrhagic fever with renal syndrome. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doi.org/10.1371/journal.pntd.0002076 https://doaj.org/article/18ee394ead074caa80b7580014a346c0 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 7, Iss 2, p e2076 (2013) |
op_relation |
http://europepmc.org/articles/PMC3585118?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002076 https://doaj.org/article/18ee394ead074caa80b7580014a346c0 |
op_doi |
https://doi.org/10.1371/journal.pntd.0002076 |
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PLoS Neglected Tropical Diseases |
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7 |
container_issue |
2 |
container_start_page |
e2076 |
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