HLA-A2 and B35 restricted hantaan virus nucleoprotein CD8+ T-cell epitope-specific immune response correlates with milder disease in hemorrhagic fever with renal syndrome.
HLA-A2 and B35 restricted hantaan virus nucleoprotein CD8+ T-cell epitope-specific immune response correlates with milder disease in hemorrhagic fever with renal syndrome.
复制标题
HLA-A2 和 B35 限制性汉滩病毒核蛋白 CD8 T 细胞表位特异性免疫反应与肾综合征出血热的较轻疾病相关
DOI：
10.1371/journal.pntd.0002076
复制
发表时间：
2013
影响因子：
3.8
通讯作者：
Jin B
中科院分区：
文献类型：
--
作者：
Ma Y;Wang J;Yuan B;Wang M;Zhang Y;Xu Z;Zhang C;Zhang Y;Liu B;Yi J;Yang K;Yang A;Zhuang R;Jin B
背景汉滩病毒（HTNV）感染是亚洲严重的公共卫生问题。HTNV结构蛋白T细胞活化肽疫苗是一种很有前途的免疫治疗方法。然而，由HLA等位基因限制的HTNV的T细胞表位和HTNV感染后表位特异性T细胞应答的作用仍然在很大程度上未被探索。方法/主要发现应用干扰素-γ酶联免疫斑点试验对37例住院期间感染汉滩病毒的患者的汉滩病毒核蛋白的5个保守的新的CD 8 + T细胞表位进行了鉴定，这些表位受中国汉族人群中最常见的HLA等位基因限制。选择分别受HLA-A2和B35限制的两个表位aa 129-aa 137和aa 131-aa 139来评估表位特异性CD 8 + T细胞应答。HLA-肽五聚体复合物染色显示患者中可检测到单个表位特异性CD 8 + T细胞的频率（aa 129-aa 137的95%置信区间为0.080%-0.208%; aa 131-aa 139的95%置信区间为0.030%-0.094%）。表位特异性五聚体+CD 8 + T细胞反应的频率在轻/中度患者中显著高于在疾病的急性期的重度/危重患者。此外，表位特异性CD 8 + T细胞在急性期的频率与血清肌酐峰值水平呈负相关，与住院期间血小板计数的最低值呈正相关。细胞内细胞因子染色和增殖实验表明，有效表位特异性CD 8 + T细胞具有产生γ-干扰素、表达CD 69和增殖能力强的特点。结论新的HLA-I类限制性HTNV核蛋白表位特异性CD 8 + T细胞反应与疾病的进展和严重程度密切相关，这可能为开发有效的HTNV肽疫苗迈出第一步。
Background Hantaan virus (HTNV) infection in humans is a serious public health concern in Asia. A potent T cell activation peptide vaccine from HTNV structure protein represents a promising immunotherapy for disease control. However, the T cell epitopes of the HTNV restricted by the HLA alleles and the role of epitope-specific T cell response after HTNV infection remain largely unexplored. Methodology/Principal Findings Five well-conserved novel CD8+ T-cell epitopes of the HTNV nucleoprotein restricted by the most popular HLA alleles in Chinese Han population were defined with interferon-γ enzyme-linked immunospot assay in 37 patients infected with HTNV during hospitalization. Two epitopes aa129–aa137 and aa131–aa139 restricted by HLA-A2 and B35, respectively, were selected to evaluate the epitope-specific CD8+ T-cell response. HLA-peptide pentamer complex staining showed that the frequency of single epitope-specific CD8+ T cell could be detected in patients (95% confidence interval for aa129–aa137: 0.080%–0.208%; for aa131–aa139: 0.030%–0.094%). The frequency of epitope-specific pentamer+ CD8+ T-cell response was much higher in mild/moderate patients than in severe/critical ones at the acute stage of the disease. Moreover, the frequency of epitope-specific CD8+ T cells at acute stage was inversely associated with the peak level of serum creatinine and was positively associated with the nadir platelet counts during the hospitalization. The intracellular cytokine staining and the proliferation assay showed that the effective epitope-specific CD8+ T cells were characterized with the production of interferon-γ, expression of CD69 and the strong capacity of proliferation. Conclusion/Significance The novel HLA class I restricted HTNV nucleoprotein epitopes-specific CD8+ T-cell responses would be closely related with the progression and the severity of the disease, which could provide the first step toward effective peptide vaccine development against HTNV infection in humans.
登录
查看更多内容
影响因子：
158.5
作者：
DUCHIN, JS;KOSTER, FT;MCDADE, J
通讯作者：
MCDADE, J
影响因子：
5.4
作者：
Nicacio, CD;Della Valle, MG;Lundkvist, Å
通讯作者：
Lundkvist, Å
影响因子：
6.7
作者：
Manigold T;Mori A;Graumann R;Llop E;Simon V;Ferrés M;Valdivieso F;Castillo C;Hjelle B;Vial P
通讯作者：
Vial P
HLA基因多态性与中国汉族人群感染汉滩病毒后病情严重程度密切相关。
影响因子：
--
作者：
Ma Y;Yuan B;Yi J;Zhuang R;Wang J;Zhang Y;Xu Z;Zhang Y;Liu B;Wei C;Zhang C;Yang A;Jin B
通讯作者：
Jin B
影响因子：
4.4
作者：
Mongkolsapaya, Juthathip;Duangchinda, Thaneeya;Screaton, Gavin
通讯作者：
Screaton, Gavin