The CD8+ T-cell response to lymphocytic choriomeningitis virus involves the L antigen:: Uncovering new tricks for an old virus
The CD8+ T-cell response to lymphocytic choriomeningitis virus involves the L antigen:: Uncovering new tricks for an old virus
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DOI：
10.1128/jvi.02632-06
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发表时间：
2007-05-01
影响因子：
5.4
通讯作者：
Sette, Alessandro
中科院分区：
文献类型：
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作者：
Kotturi, Maya F.;Peters, Bjoern.;Sette, Alessandro
CD 8（+）T细胞反应控制H-2（B）小鼠淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染尽管对LCW感染的抗原特异性应答进行了充分的研究，但我们发现H-2（B）小鼠中对LCMV的CD 8（+）CD 44（hi）T细胞应答的显著部分不是由已知表位引起的。我们筛选了预测结合主要组织相容性复合物I类的肽和跨越完整LCW蛋白质组的重叠15聚体肽，用于从来自LCW感染的H-2（B）小鼠的CD 8（+）T细胞诱导γ干扰素（IFN-γ）。我们发现了19个新的表位。与先前已知的9个表位一起，这些表位解释了总的CD 8（+）CD 44（hi）应答。因此，旁观者T细胞活化对CD 8（+）CD 44（hi）库没有明显贡献。引人注目的是，19个新表位中有15个来自病毒L聚合酶，到目前为止，它还没有被认为是LCW感染诱导的细胞反应的靶点。L表位诱导体内细胞毒性的显着水平，并赋予针对LCMV攻击的保护。有趣的是，对病毒攻击的保护与CD 8（+）T细胞的细胞溶解潜力最相关，而IFN-γ的产生和肽亲和力似乎起着较小的作用。总之，这些发现表明LCW特异性CD 8（+）T细胞反应比以前认识到的更复杂。
CD8(+) T-cell responses control lymphocytic choriomeningitis virus (LCMV) infection in H-2(b) mice. Although antigen-specific responses against LCW infection are well studied, we found that a significant fraction of the CD8(+) CD44(hi) T-cell response to LCMV in H-2(b) mice was not accounted for by known epitopes. We screened peptides predicted to bind major histocompatibility complex class I and overlapping 15-mer peptides spanning the complete LCW proteome for gamma interferon (IFN-gamma) induction from CD8(+) T cells derived from LCW-infected H-2(b) mice. We identified 19 novel epitopes. Together with the 9 previously known, these epitopes account for the total CD8(+) CD44(hi) response. Thus, bystander T-cell activation does not contribute appreciably to the CD8(+) CD44(hi) pool. Strikingly, 15 of the 19 new epitopes were derived from the viral L polymerase, which, until now, was not recognized as a target of the cellular response induced by LCW infection. The L epitopes induced significant levels of in vivo cytotoxicity and conferred protection against LCMV challenge. Interestingly, protection from viral challenge was best correlated with the cytolytic potential of CD8(+) T cells, whereas IFN-gamma production and peptide avidity appear to play a lesser role. Taken together, these findings illustrate that the LCW-specific CD8(+) T-cell response is more complex than previously appreciated.