Department of Immunology and Microbiology, University of Copenhagen, DK-2200 Copenhagen, Denmark.
Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA.
Viruses. 2022 Mar 14;14(3):601. doi: 10.3390/v14030601.
Understanding the complexity of the T-cell epitope hierarchy in humans through mouse models can be difficult. In particular, using only one murine strain, the C57BL/6 mouse, to investigate the immune response to influenza virus infection limits our understanding. In the present study, by immunizing C57BL/6 mice with an adenoviral vector encoding the polymerase acidic (AdIiPA) protein of influenza A virus, we were able to induce a high number of PA-specific T cells. However, upon challenge, these cells were only partly protective. When instead immunizing BALB/c mice with AdIiPA, we found that the immunized mice were fully protected against challenge. We found that this protection was dependent on CD8 T cells, and we identified a novel H-2D-restricted epitope, PA33. These findings provide a new tool for researchers to study PA-specific immunity in mice with an H-2 haplotype. Additionally, our findings underscore the importance of critically evaluating important limitations of using a single inbred mouse strain in vaccine studies.
通过小鼠模型来理解人类 T 细胞表位层次结构的复杂性可能很困难。特别是，仅使用一种小鼠品系（C57BL/6 小鼠）来研究流感病毒感染的免疫反应，限制了我们的理解。在本研究中，我们通过用编码流感 A 病毒聚合酶酸性（AdIiPA）蛋白的腺病毒载体免疫 C57BL/6 小鼠，成功地诱导了大量的 PA 特异性 T 细胞。然而，在受到挑战时，这些细胞只有部分保护作用。当我们用 AdIiPA 免疫 BALB/c 小鼠时，发现免疫的小鼠完全免受挑战。我们发现这种保护作用依赖于 CD8 T 细胞，并且我们鉴定出一个新的 H-2D 限制性表位，PA33。这些发现为研究具有 H-2 单倍型的小鼠中 PA 特异性免疫提供了新工具。此外，我们的研究结果强调了在疫苗研究中批判性地评估使用单一近交系小鼠品系的重要性。
