Diversity in the acute CD8 T cell response to vaccinia virus in humans
Diversity in the acute CD8 T cell response to vaccinia virus in humans
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DOI：
10.4049/jimmunol.175.11.7550
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发表时间：
2005-12-01
影响因子：
4.4
通讯作者：
Koelle, DM
中科院分区：
文献类型：
--
作者：
Jing, LC;Chong, TM;Koelle, DM
正痘病毒具有复杂的蛋白质组。感染引起活跃的CD8应答，这在某些系统中是从原发感染中恢复所需的。关于CD8 T细胞识别的Ag和表位知之甚少。我们通过表达来自牛痘基因组DNA文库的多肽片段来检测克隆的和大量的人牛痘特异性CD8 CTL的精细特异性。这种表位发现方法强调病毒特异性生物活性，因为应答细胞都与整个牛痘病毒反应。在不同的牛痘开放阅读框中，将16个受几个HLA A和B等位基因限制的新表位定义为Nomamer肽水平。另外7个表位被定位到牛痘蛋白的短区域。CD8应答的靶点包括分配给结构、酶、转录因子和免疫逃避功能的蛋白质，并包括所有病毒动力学类别的成员。大多数表位在其他正痘病毒中是保守的。在单一血液样本中检测到对至少18个表位的反应，揭示了令人惊讶的多样性程度。这些表位将是有用的，在自然史研究中的CD8的反应，牛痘，一种非持久性病毒与长期记忆，并在设计和评估的减毒和复制能力差的牛痘病毒株进行测试天花和猴痘预防和异源抗原的交付。
Orthopoxviruses have complex proteomes. Infection provokes a brisk CD8 response, which is required in some systems for recovery from primary infection. Little is known concerning the Ags and epitopes recognized by CD8 T cells. We examined the fine specificity of cloned and bulk human vaccinia-specific CD8 CTL by expressing polypeptide fragments from a library of vaccinia genomic DNA. This epitope discovery method emphasizes virus-specific biological activity, as the responder cells are all reactive with whole vaccinia virus. Sixteen novel epitopes, restricted by several HLA A and B alleles, were defined to the nomamer peptide level in diverse vaccinia open reading frames. An additional seven epitope were mapped to short regions of vaccinia proteins. Targets of the CD8 response included proteins assigned to structural, enzymatic, transcription factor, and immune evasion functions, and included members of all viral kinetic classes. Most epitopes were conserved in other orthopoxviruses. Responses to at least 18 epitopes were detected within a single blood sample, revealing a surprising degree of diversity. These epitopes will be useful in natural history studies of CD8 responses to vaccinia, a nonpersisting virus with long-term memory, and in the design and evaluation of attenuated and replication-incompetent vaccinia strains being tested for variola and monkeypox prevention and for the delivery of heterologous Ags.