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在亚洲人群中,保守表位主导了针对甲型 H1N1 流感病毒的交叉 CD8+ T 细胞反应。

Conserved epitopes dominate cross-CD8+ T-cell responses against influenza A H1N1 virus among Asian populations.

机构信息

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.

出版信息

Eur J Immunol. 2013 Aug;43(8):2055-69. doi: 10.1002/eji.201343417. Epub 2013 Jun 14.


DOI:10.1002/eji.201343417
PMID:23681926
Abstract

Novel strains of influenza A viruses (IAVs) have emerged with high infectivity and/or pathogenicity in recent years, causing worldwide concern. T cells are correlated with protection in humans through cross-reactive immunity against heterosubtypes of IAV. However, the different hierarchical roles of IAV-derived epitopes with distinct levels of polymorphism in the cross-reactive T-cell responses against IAV remain elusive. In this study, immunodominant epitopes scattered throughout the entire proteome of 2009 pandemic influenza A H1N1 virus and seasonal IAVs were synthesized and divided into different pools depending on their conservation. The overall profile of the IAV-specific CD8(+) T-cell immunity was detected by utilizing these peptide pools and also individual peptides. A dominant role of the conserved peptide-specific T-cell immunity was illuminated within the anti-IAV responses, while the CD8(+) T-cell responses against the variable epitopes were lower than the conserved peptides. As previously demonstrated within a Caucasian population, we determined that GL9-specific T cells, which also utilize Vβ 17 TCR (BV19), play a pivotal role in IAV-specific T-cell immunity within an HLA-A2(+) Asian population. Our study objectively reveals the different predominant roles of T-cell epitopes among IAV-specific cross-reactive cellular immunity. This may guide the development of vaccines with cross-T-cell immunogenicity against heterosubtypes of IAV.

摘要

近年来,新型甲型流感病毒(IAV)具有高传染性和/或致病性,引起了全球关注。T 细胞通过对 IAV 异亚型的交叉反应性免疫与人类的保护相关。然而,IAV 衍生表位在针对 IAV 的交叉反应性 T 细胞反应中的不同层次作用仍不清楚,这些表位具有不同程度的多态性。在这项研究中,我们合成了 2009 年大流行的甲型 H1N1 流感病毒和季节性 IAV 整个蛋白质组中散布的免疫优势表位,并根据其保守性将它们分为不同的池。通过利用这些肽池和单个肽,检测了针对 IAV 的特异性 CD8(+) T 细胞免疫的总体特征。在抗 IAV 反应中,保守肽特异性 T 细胞免疫起着主导作用,而针对可变表位的 CD8(+) T 细胞反应低于保守肽。正如在白种人群中所证明的那样,我们确定了 GL9 特异性 T 细胞(也利用 Vβ17TCR(BV19))在 HLA-A2(+)亚洲人群中 IAV 特异性 T 细胞免疫中起着关键作用。我们的研究客观地揭示了 IAV 特异性交叉反应性细胞免疫中 T 细胞表位的不同主要作用。这可能指导针对 IAV 异亚型的具有交叉 T 细胞免疫原性的疫苗的开发。

相似文献

[1]
Conserved epitopes dominate cross-CD8+ T-cell responses against influenza A H1N1 virus among Asian populations.

Eur J Immunol. 2013-6-14

[2]
Severity of Acute Infectious Mononucleosis Correlates with Cross-Reactive Influenza CD8 T-Cell Receptor Repertoires.

mBio. 2017-12-5

[3]
The design and proof of concept for a CD8(+) T cell-based vaccine inducing cross-subtype protection against influenza A virus.

Immunol Cell Biol. 2012-11-13

[4]
Variation at Extra-epitopic Amino Acid Residues Influences Suppression of Influenza Virus Replication by M1 Epitope-Specific CD8 T Lymphocytes.

J Virol. 2018-5-14

[5]
Precursor frequency and competition dictate the HLA-A2-restricted CD8+ T cell responses to influenza A infection and vaccination in HLA-A2.1 transgenic mice.

J Immunol. 2011-7-15

[6]
HLA-B*27:05 alters immunodominance hierarchy of universal influenza-specific CD8+ T cells.

PLoS Pathog. 2020-8-4

[7]
Identification of immunogenic consensus T-cell epitopes in globally distributed influenza-A H1N1 neuraminidase.

Infect Genet Evol. 2010-11-19

[8]
Universal H1N1 influenza vaccine development: identification of consensus class II hemagglutinin and neuraminidase epitopes derived from strains circulating between 1980 and 2011.

Hum Vaccin Immunother. 2013-7-11

[9]
Human T-cells directed to seasonal influenza A virus cross-react with 2009 pandemic influenza A (H1N1) and swine-origin triple-reassortant H3N2 influenza viruses.

J Gen Virol. 2012-11-14

[10]
Broad-Based Influenza-Specific CD8 T Cell Response without the Typical Immunodominance Hierarchy and Its Potential Implication.

Viruses. 2021-6-5

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[2]
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[3]
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J Virol. 2024-1-23

[4]
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[5]
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[6]
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[7]
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[8]
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Influenza Other Respir Viruses. 2023-1

[9]
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[10]
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