Identification of multiple simian immunodeficiency virus (SIV)-specific CTL epitopes in sooty mangabeys with natural and experimentally acquired SIV infection
Identification of multiple simian immunodeficiency virus (SIV)-specific CTL epitopes in sooty mangabeys with natural and experimentally acquired SIV infection
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DOI：
10.4049/jimmunol.164.2.934
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发表时间：
2000-01-15
影响因子：
4.4
通讯作者：
Johnson, RP
中科院分区：
文献类型：
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作者：
Kaur, A;Yang, J;Johnson, RP
宿主对SIV感染的免疫反应可能是这些非人灵长类动物如何维持无症状慢病毒感染的重要决定因素。我们以前描述了两种无症状SIV感染的模式：在SIVmac239感染的白眉猴中，低病毒载量具有强烈的SIV特异性CTL活性，而在天然感染的白眉猴中，高病毒载量具有通常弱的或不存在的SIV特异性CTL活性。为了确定SIV感染的白眉猴中CTL应答的特异性，结果表明，与SIVmac239感染的白眉猴相比，自然感染的白眉猴的SIV特异性CTL克隆产量显著降低。所有CTL克隆均为表型CD3（+）CD8（+），裂解受MHC限制。在5只白眉猴中鉴定出7个SIV CTL表位：Gag中1个，Nef和Env中各3个。CTL表位定位于SIV基因组中的保守区域，并且是免疫显性的。自然感染和SIVmac239感染的白眉猴都能识别出几个相似或相同的CTL表位，它们都具有I类MHC等位基因。据我们所知，这是首次报道SIV特异性CTL表位在正常白眉猴中的存在。
Host immune responses to SIV infection in sooty mangabeys are likely to be an important determinant of how such nonhuman primate species maintain asymptomatic lentivirus infection. We have previously described two patterns of asymptomatic SIV infection in sooty mangabeys: low viral loads with vigorous SIV-specific CTL activity in SIVmac239-infected sooty mangabeys, and high viral loads with generally weak or absent SIV-specific CTL activity in naturally infected sooty mangabeys, To define the specificity of the CTL response in SIV-infected mangabeys, we characterized CTL epitopes in two naturally infected and three SIVmac239-infected sooty mangabeys, Compared with that in SIVmac239-infected mangabeys, the yield of SIV-specific CTL clones was significantly lower in naturally infected sooty mangabeys. All CTL clones were phenotypically CD3(+) CD8(+), and lysis was MHC restricted. Seven SIV CTL epitopes were identified in five sooty mangabeys: one in Gag and three each in Nef and Envelope (Env). The CTL epitopes mapped to conserved regions in the SIV genome and were immunodominant. Several similar or identical CTL epitopes were recognized by both naturally infected and SIVmac239-infected mangabeys that shared class I MHC alleles, To our knowledge, this is the first report of SIV-specific CTL epitopes in sooty mangabeys, Longitudinal studies of viral load and sequence variation in CTL epitopes may provide useful information on the role of CTL in control or persistence of sn infection in sooty mangabeys.