HLA-A*0201, HLA-A*1101, and HLA-B*0702 transgenic mice recognize numerous poxvirus determinants from a wide variety of viral gene products
HLA-A*0201, HLA-A*1101, and HLA-B*0702 transgenic mice recognize numerous poxvirus determinants from a wide variety of viral gene products
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DOI：
10.4049/jimmunol.175.8.5504
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发表时间：
2005-10-15
影响因子：
4.4
通讯作者：
Sette, A
中科院分区：
文献类型：
--
作者：
Pasquetto, V;Bui, HH;Sette, A
在小鼠中详细探索的病毒模型中，CTL通常集中在一些免疫显性决定簇上。在这项研究中，我们使用多管齐下的方法来了解对牛痘病毒的CTL反应的多样性，牛痘病毒是一种原型痘病毒，其基因组比通常在小鼠中研究的模型RNA病毒的基因组大20倍。基于肽与HLA超型结合的预测计算算法，我们合成了一组2889个肽，开始创建人对痘病毒的CTL应答的免疫组学图谱。使用这个面板与CTL从牛痘病毒感染的HLA转基因小鼠，我们确定了14个HLA-A*0201-，4个HLA-A*1101-和3个HLA-B*0702-限制性CD 8（+）T细胞决定簇分布在20个不同的蛋白质。这些肽能够以病毒决定簇的典型亲和力结合一个或多个A2、A3和B7超型分子。令人惊讶的是，除了预期的早期中间基因产物之外，许多被识别的病毒蛋白被预测为晚期基因产物。几乎所有确定的决定因素都有相同的对应物，由改良的安卡拉牛痘病毒和天花病毒编码。这些发现对设计新的天花疫苗和理解对大DNA病毒的免疫反应具有重要意义。
In virus models explored in detail in mice, CTL typically focus on a few immunodominant determinants. In this study we use a multipronged approach to understand the diversity of CTL responses to vaccinia virus, a prototypic poxvirus with a genome similar to 20-fold larger than that of the model RNA viruses typically studied in mice. Based on predictive computational algorithms for peptide binding to HLA supertypes, we synthesized a panel of 2889 peptides to begin to create an immunomic map of human CTL responses to poxviruses. Using this panel in conjunction with CTLs from vaccinia virus-infected HLA transgenic mice, we identified 14 HLA-A*0201-, 4 HLA-A*1101-, and 3 HLA-B*0702-restricted CD8(+) T cell determinants distributed over 20 distinct proteins. These peptides were capable of binding one or multiple A2, A3, and B7 supertype molecules with affinities typical of viral determinants. Surprisingly, many of the viral proteins recognized are predicted to be late gene products, in addition to the early intermediate gene products expected. Nearly all of the determinants identified have identical counterparts encoded by modified vaccinia virus Ankara as well as variola virus, the agent of smallpox. These findings have implications for the design of new smallpox vaccines and the understanding of immune responses to large DNA viruses in general.