Immunoprotectivity of HLA-A2 CTL peptides derived from respiratory syncytial virus fusion protein in HLA-A2 transgenic mouse.
Immunoprotectivity of HLA-A2 CTL peptides derived from respiratory syncytial virus fusion protein in HLA-A2 transgenic mouse.
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DOI：
10.1371/journal.pone.0025500
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Chow YH
中科院分区：
文献类型：
--
作者：
Shao HY;Lin YW;Yu SL;Lin HY;Chitra E;Chang YC;Sia C;Chong P;Hsu MT;Wei OL;Chow YH
鉴定hla限制性CD8+ T细胞表位对研究rsv诱导的免疫和疾病具有重要意义。我们通过算法分析呼吸道合胞病毒（RSV）融合蛋白(F)的序列，合成了可能与HLA-A*0201结合的合成肽。测试的25个9-mer肽中有4个：肽3 （F33-41）、13 （F214-222）、14 （F273-281）和23 （F559-567）与HLA-A*0201有中高亲和力结合，能够诱导经RSV或表达RSV f的重组腺病毒免疫的转HLA-A*0201的小鼠淋巴细胞分泌IFN-γ和IL-2，并在体外二次召回中诱导Th1和CD8+ T细胞应答。观察到这些肽诱导的效应反应对RSV活体攻击具有不同的保护作用。这些肽也能较好地恢复RSV诱导的体重减轻。在用肽23免疫的小鼠中，观察到肺部病毒载量的显著降低，这似乎增加了炎症趋化因子（CCL17、CCL22和IL-18）的水平，但没有增加肺部嗜酸性粒细胞的浸润。然而，经肽13预先免疫的小鼠，RSV感染诱导的浸润性嗜酸性粒细胞明显减少。我们的研究结果表明，RSV F蛋白的hla - a2限制性表位可能有助于基于表位的RSV疫苗的开发。
Identification of HLA-restricted CD8+ T cell epitopes is important to study RSV-induced immunity and illness. We algorithmically analyzed the sequence of the fusion protein (F) of respiratory syncytial virus (RSV) and generated synthetic peptides that can potentially bind to HLA-A*0201. Four out of the twenty-five 9-mer peptides tested: peptides 3 (F33–41), 13 (F214–222), 14 (F273–281), and 23 (F559–567), were found to bind to HLA-A*0201 with moderate to high affinity and were capable of inducing IFN-γ and IL-2 secretion in lymphocytes from HLA-A*0201 transgenic (HLA-Tg) mice pre-immunized with RSV or recombinant adenovirus expressing RSV F. HLA-Tg mice were immunized with these four peptides and were found to induce both Th1 and CD8+ T cell responses in in vitro secondary recall. Effector responses induced by these peptides were observed to confer differential protection against live RSV challenge. These peptides also caused better recovery of body weight loss induced by RSV. A significant reduction of lung viral load was observed in mice immunized with peptide 23, which appeared to enhance the levels of inflammatory chemokines (CCL17, CCL22, and IL-18) but did not increase eosinophil infiltration in the lungs. Whereas, significant reduction of infiltrated eosinophils induced by RSV infection was found in mice pre-immunized with peptide 13. Our results suggest that HLA-A2-restricted epitopes of RSV F protein could be useful for the development of epitope-based RSV vaccine.
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DOI：
10.4049/jimmunol.1000423
发表时间：
2010-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Fulton RB;Meyerholz DK;Varga SM
通讯作者：
Varga SM
影响因子：
5.4
作者：
Goulder, PJR;Lechner, F;Walker, BD
通讯作者：
Walker, BD
影响因子：
1.6
作者：
Agenbach, E;Tiemessen, CT;Venter, M
通讯作者：
Venter, M
影响因子：
--
作者：
CHANOCK, R;FINBERG, L
通讯作者：
FINBERG, L
影响因子：
5.4
作者：
CHERRIE, AH;ANDERSON, K;OPENSHAW, PJM
通讯作者：
OPENSHAW, PJM