Norovirus-Specific Memory T Cell Responses in Adult Human Donors.
Norovirus-Specific Memory T Cell Responses in Adult Human Donors.
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DOI：
10.3389/fmicb.2016.01570
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发表时间：
2016
影响因子：
5.2
通讯作者：
Blazevic V
中科院分区：
文献类型：
--
作者：
Malm M;Tamminen K;Vesikari T;Blazevic V
诺如病毒（NoV）是全球所有年龄段人群急性胃肠炎的主要原因。已经彻底研究了阻断NoV病毒样颗粒（VLP）与细胞受体结合的NoV特异性血清抗体。相比之下，只有少数出版物可用于自然感染病毒的人类中的NoV衣壳VP1蛋白特异性T细胞应答。将先前暴露于NoV的8名健康成人供体的新鲜分离的外周血单核细胞用来源于NoV GII.4 - 1999、GII.4 - 2012（Sydney）和GI.3的纯化VLP刺激，并通过ELISPOT测定测量IFN-γ产生。此外，将跨越GII.4 VP1的整个539个氨基酸序列的76个重叠合成肽合并到二维矩阵中，并用于鉴定推定的T细胞表位。八名受试者中的七名响应于肽产生IFN-γ，五名受试者响应于相同来源的VLP产生IFN-γ。通常，与VLP相比，在每个供体中用肽诱导更强的T细胞应答。在两名受试者中鉴定了VP1（134SPSQVTMFPHIIVDVRQL 151）的壳结构域中的CD8 + T细胞表位，这两名受试者都具有人白细胞抗原（HLA）-A β 02：01等位基因。据我们所知，这是第一份使用合成肽研究人类受试者中的NoV特异性T细胞应答并鉴定T细胞表位的报告。
Norovirus (NoV) is a leading cause of acute gastroenteritis in people of all ages worldwide. NoV-specific serum antibodies which block the binding of NoV virus-like particles (VLPs) to the cell receptors have been thoroughly investigated. In contrast, only a few publications are available on the NoV capsid VP1 protein-specific T cell responses in humans naturally infected with the virus. Freshly isolated peripheral blood mononuclear cells of eight healthy adult human donors previously exposed to NoV were stimulated with purified VLPs derived from NoV GII.4-1999, GII.4-2012 (Sydney), and GI.3, and IFN-γ production was measured by an ELISPOT assay. In addition, 76 overlapping synthetic peptides spanning the entire 539-amino acid sequence of GII.4 VP1 were pooled into two-dimensional matrices and used to identify putative T cell epitopes. Seven of the eight subjects produced IFN-γ in response to the peptides and five subjects produced IFN-γ in response to the VLPs of the same origin. In general, stronger T cell responses were induced with the peptides in each donor compared to the VLPs. A CD8+ T cell epitope in the shell domain of the VP1 (134SPSQVTMFPHIIVDVRQL151) was identified in two subjects, both having human leukocyte antigen (HLA)-A∗02:01 allele. To our knowledge, this is the first report using synthetic peptides to study NoV-specific T cell responses in human subjects and identify T cell epitopes.