CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Graduate University, Beijing, China.
J Infect Dis. 2010 Oct 15;202(8):1171-80. doi: 10.1086/656315.
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.
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).
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.
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.
严重急性呼吸系统综合症冠状病毒（SARS-CoV）于 2002 年爆发，具有高度传染性和危及生命的特点，至今仍然是未来爆发的潜在风险。膜（M）和包膜（E）蛋白是 SARS-CoV 的主要结构蛋白。M 蛋白已被确定为体液免疫反应中的保护性抗原。然而，其在刺激细胞免疫方面的潜在作用仍不清楚。
在这项研究中，通过体外重折叠、T2 细胞结合试验以及在 HLA-A2.1/K(b)转基因小鼠和人外周血单核细胞（PBMC）中刺激细胞毒性 T 淋巴细胞（CTL）表位，对源自 M 和 E 蛋白的肽进行了测试。
鉴定出源自 M 蛋白的九肽 Mn2 和十肽 Md3 作为其特异性 CTL 表位，并用于评估 M 蛋白的特异性免疫。在从 SARS 感染中康复的供体的 PBMC 中发现了对 M 蛋白特异性 CTL 表位刺激的反应。此外，通过对 Mn2 和 Md3 重叠的一系列截短肽的免疫原性和结构分析，M 蛋白的跨膜区可能含有一个 T 细胞表位簇。
SARS-CoV 的 M 蛋白具有主导的细胞免疫原性。这一点，加上之前关于对 M 蛋白产生强烈体液免疫反应的报道，可能有助于进一步解释 SARS 的免疫原性，并为 SARS-CoV 疫苗设计提供潜在目标。
