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首页> 外文期刊>The Journal of Infectious Diseases >The membrane protein of severe acute respiratory syndrome coronavirus acts as a dominant immunogen revealed by a clustering region of novel functionally and structurally defined cytotoxic T-lymphocyte epitopes.
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The membrane protein of severe acute respiratory syndrome coronavirus acts as a dominant immunogen revealed by a clustering region of novel functionally and structurally defined cytotoxic T-lymphocyte epitopes.

机译:严重的急性呼吸系统综合症冠状病毒的膜蛋白起着主要的免疫原的作用,这是由功能和结构上新颖的细胞毒性T淋巴细胞表位的聚集区域揭示的。

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BACKGROUND: Severe acute respiratory syndrome coronavirus (SARS-CoV), which emerged with highly contagious and life-threatening characteristics in 2002, remains a potential risk for future outbreaks. Membrane (M) and envelope (E) proteins are major structural proteins of the SARS-CoV. The M protein has been determined as a protective antigen in humoral responses. However, its potential roles in stimulating cellular immunity remain elusive. METHODS: In this study, a panel of peptides derived from M and E proteins were tested by in vitro refolding, T2 cell-binding assays, and responses stimulated by cytotoxic T-lymphocyte (CTL) epitopes in HLA-A2.1/K(b) transgenic mice and human peripheral blood mononuclear cells (PBMCs). RESULTS: A nonameric epitope Mn2 and a decameric epitope Md3 derived from the M protein were identified and used for the evaluation of M protein-specific immunity. Responses stimulated by M protein-specific CTL epitopes have been found in the PBMCs of donors who had recovered from SARS infection. Additionally, the transmembrane domain of the M protein may contain a T cell epitope cluster revealed by the immunogenic and structural analysis of a panel of truncated peptides overlapping with Mn2 and Md3. CONCLUSIONS: The M protein of SARS-CoV holds dominant cellular immunogenicity. This, together with previous reports of a strong humoral response against the M protein, may help to further explain the immunogenicity of SARS and serves as potential targets for SARS-CoV vaccine design.
机译:背景:严重急性呼吸系统综合症冠状病毒(SARS-CoV)于2002年出现,具有极强的传染性和威胁生命的特征,仍然是未来爆发的潜在风险。膜蛋白(M)和包膜蛋白(E)是SARS-CoV的主要结构蛋白。 M蛋白已被确定为体液反应中的保护性抗原。然而,其在刺激细胞免疫中的潜在作用仍然难以捉摸。方法:在这项研究中,通过体外重折叠,T2细胞结合测定以及HLA-A2.1 / K中细胞毒性T淋巴细胞(CTL)表位刺激的应答,测试了一组由M和E蛋白衍生的肽。 b)转基因小鼠和人外周血单核细胞(PBMC)。结果:鉴定出了由M蛋白衍生的非异构抗原决定簇Mn2和十聚抗原决定簇Md3,并用于评估M蛋白特异性免疫。已从SARS感染中恢复的供体的PBMC中发现了M蛋白特异性CTL表位刺激的反应。另外,M蛋白的跨膜结构域可以包含T细胞表位簇,该簇由通过与Mn2和Md3重叠的一组截短的肽的免疫原性和结构分析揭示。结论:SARS冠状病毒的M蛋白具有显着的细胞免疫原性。这与先前针对M蛋白的强烈体液应答的报道一起,可能有助于进一步解释SARS的免疫原性,并作为SARS-CoV疫苗设计的潜在靶标。

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