MHC class I-presented T cell epitopes identified by immunoproteomics analysis are targets for a cross reactive influenza-specific T cell response.
MHC class I-presented T cell epitopes identified by immunoproteomics analysis are targets for a cross reactive influenza-specific T cell response.
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DOI：
10.1371/journal.pone.0048484
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Philip R
中科院分区：
文献类型：
--
作者：
Testa JS;Shetty V;Hafner J;Nickens Z;Kamal S;Sinnathamby G;Philip R
流感病毒感染及其引起的并发症是一个重大的全球公共卫生问题。提高对流感的体液免疫是当前常规流感疫苗的目标，然而，这些疫苗通常不具有交叉保护性。相反，由原发性流感感染产生的细胞介导的免疫提供了针对血清学上不同的病毒的实质性保护，这是由于识别交叉反应性T细胞表位，通常来自病毒亚型之间保守的内部病毒蛋白。目前正在努力开发一种通用的流感疫苗，这种疫苗将刺激体液和细胞免疫反应，从而产生长寿记忆。这样的通用疫苗应该靶向保守的流感病毒抗体和T细胞表位，这些表位在毒株之间没有变化。在过去的十年中，免疫蛋白质组学，或HLA I类呈递表位的直接鉴定，已经成为用于鉴定T细胞表位的基序预测方法的替代方法。在这项研究中，我们使用这种方法来揭示几个交叉特异性的MHC I类特异性T细胞表位自然提出的流感病毒A感染的细胞。当这些保守的T细胞表位与来自流感M2的胞外域的交叉反应性抗体表位组合时，产生跨毒株特异性细胞介导的和体液免疫。总之，我们已经证明保守的表位特异性CTL可以识别多种流感病毒株感染的靶细胞，并且当与通用抗体表位组合时，可以产生病毒特异性体液和T细胞应答，这是迈向通用疫苗概念的一步。这些表位也有可能作为新的工具来表征流感感染中的T细胞免疫，并可能作为通用疫苗候选物的一部分，以补充目前的疫苗。
Influenza virus infection and the resulting complications are a significant global public health problem. Improving humoral immunity to influenza is the target of current conventional influenza vaccines, however, these are generally not cross-protective. On the contrary, cell-mediated immunity generated by primary influenza infection provides substantial protection against serologically distinct viruses due to recognition of cross-reactive T cell epitopes, often from internal viral proteins conserved between viral subtypes. Efforts are underway to develop a universal flu vaccine that would stimulate both the humoral and cellular immune responses leading to long-lived memory. Such a universal vaccine should target conserved influenza virus antibody and T cell epitopes that do not vary from strain to strain. In the last decade, immunoproteomics, or the direct identification of HLA class I presented epitopes, has emerged as an alternative to the motif prediction method for the identification of T cell epitopes. In this study, we used this method to uncover several cross-specific MHC class I specific T cell epitopes naturally presented by influenza A-infected cells. These conserved T cell epitopes, when combined with a cross-reactive antibody epitope from the ectodomain of influenza M2, generate cross-strain specific cell mediated and humoral immunity. Overall, we have demonstrated that conserved epitope-specific CTLs could recognize multiple influenza strain infected target cells and, when combined with a universal antibody epitope, could generate virus specific humoral and T cell responses, a step toward a universal vaccine concept. These epitopes also have potential as new tools to characterize T cell immunity in influenza infection, and may serve as part of a universal vaccine candidate complementary to current vaccines.
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