Nef-specific CD8+ T cell responses contribute to HIV-1 immune control.
Nef-specific CD8+ T cell responses contribute to HIV-1 immune control.
复制标题
DOI：
10.1371/journal.pone.0073117
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Matthews PC
中科院分区：
文献类型：
--
作者：
Adland E;Carlson JM;Paioni P;Kløverpris H;Shapiro R;Ogwu A;Riddell L;Luzzi G;Chen F;Balachandran T;Heckerman D;Stryhn A;Edwards A;Ndung'u T;Walker BD;Buus S;Goulder P;Matthews PC
最近在siv -猕猴HIV感染模型中的研究表明，nef特异性CD8+ t细胞反应可能介导病毒血症的高效免疫控制。在HIV感染中，Nef识别在急性感染中占主导地位，但在慢性感染受试者的大型队列研究中，T细胞对Nef反应的广度与显著的病毒控制无关。相反，改善的疾病结果与靶向Gag和在某些情况下靶向Pol有关。然而，对Nef特异性T细胞反应广度的分析一直被Nef中心区域的极端免疫原性和多个表位重叠所混淆，这使得通过ifn - γ ELISPOT检测无法区分不同的反应。因此，需要一种替代方法来评估Nef作为免疫靶点。在这里，我们在一项包含700名慢性c进化支感染患者的队列研究中发现，Nef内50%的HLA-B选择多态性与预测的病毒适应成本相关，而成功驱动Nef内选择的HLA-B等位基因与较低的病毒载量相关。此外，受保护性HLA I类等位基因限制的特异性CD8+ T细胞表位与Nef中有效的siv特异性表位基本一致。在Nef中区分这种个体hiv特异性反应需要特定的肽- mhc I四聚体。总的来说，这些数据表明CD8+ T细胞靶向某些特定的Nef表位有助于抑制HIV。这些数据表明，重新评估Nef在HIV t细胞候选疫苗中的潜在应用是合理的。
Recent studies in the SIV-macaque model of HIV infection suggest that Nef-specific CD8+ T-cell responses may mediate highly effective immune control of viraemia. In HIV infection Nef recognition dominates in acute infection, but in large cohort studies of chronically infected subjects, breadth of T cell responses to Nef has not been correlated with significant viraemic control. Improved disease outcomes have instead been associated with targeting Gag and, in some cases, Pol. However analyses of the breadth of Nef-specific T cell responses have been confounded by the extreme immunogenicity and multiple epitope overlap within the central regions of Nef, making discrimination of distinct responses impossible via IFN-gamma ELISPOT assays. Thus an alternative approach to assess Nef as an immune target is needed. Here, we show in a cohort of >700 individuals with chronic C-clade infection that >50% of HLA-B-selected polymorphisms within Nef are associated with a predicted fitness cost to the virus, and that HLA-B alleles that successfully drive selection within Nef are those linked with lower viral loads. Furthermore, the specific CD8+ T cell epitopes that are restricted by protective HLA Class I alleles correspond substantially to effective SIV-specific epitopes in Nef. Distinguishing such individual HIV-specific responses within Nef requires specific peptide-MHC I tetramers. Overall, these data suggest that CD8+ T cell targeting of certain specific Nef epitopes contributes to HIV suppression. These data suggest that a re-evaluation of the potential use of Nef in HIV T-cell vaccine candidates would be justified.
登录
查看更多内容
影响因子：
5.4
作者：
Gray, Clive M.;Mlotshwa, Mandla;Karim, Salim Abdool
通讯作者：
Karim, Salim Abdool
影响因子：
5.4
作者：
Brockman, Mark A.;Schneidewind, Arne;Allen, Todd M.
通讯作者：
Allen, Todd M.
影响因子：
64.8
作者：
Kawashima, Yuka;Pfafferott, Katja;Frater, John;Matthews, Philippa;Payne, Rebecca;Addo, Marylyn;Gatanaga, Hiroyuki;Fujiwara, Mamoru;Hachiya, Atsuko;Koizumi, Hirokazu;Kuse, Nozomi;Oka, Shinichi;Duda, Anna;Prendergast, Andrew;Crawford, Hayley;Leslie, Alasdair;Brumme, Zabrina;Brumme, Chanson;Allen, Todd;Brander, Christian;Kaslow, Richard;Tang, James;Hunter, Eric;Allen, Susan;Mulenga, Joseph;Branch, Songee;Roach, Tim;John, Mina;Mallal, Simon;Ogwu, Anthony;Shapiro, Roger;Prado, Julia G.;Fidler, Sarah;Weber, Jonathan;Pybus, Oliver G.;Klenerman, Paul;Ndung'u, Thumbi;Phillips, Rodney;Heckerman, David;Harrigan, P. Richard;Walker, Bruce D.;Takiguchi, Masafumi;Goulder, Philip
通讯作者：
Goulder, Philip
影响因子：
3.3
作者：
Foster, John L.;Garcia, J. Victor
通讯作者：
Garcia, J. Victor
影响因子：
1.5
作者：
Bredell, Helba;Martin, Darren P.;Williamson, Carolyn
通讯作者：
Williamson, Carolyn