CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Eur J Immunol. 2013 Aug;43(8):2055-69. doi: 10.1002/eji.201343417. Epub 2013 Jun 14.
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.
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。
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