Peng Hui, Yang Li-tao, Wang Ling-yun, Li Jian, Huang Jun, Lu Zhi-qiang, Koup Richard A, Bailer Robert T, Wu Chang-you
Department of Immunology, Zhongshan Medical School, Sun Yat-sen University, No. 74 Zhongshan Road II, Guangzhou 510089, China.
Virology. 2006 Aug 1;351(2):466-75. doi: 10.1016/j.virol.2006.03.036. Epub 2006 May 11.
The nucleocapsid (N) protein is a structural component of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) and can induce antibody responses in SARS patients during infection. However, it is not known whether SARS-CoV N protein can induce a long persistence of memory T-cell response in human. In this study, we found that peripheral blood mononuclear cells (PBMCs) from fully recovered SARS individuals rapidly produced IFN-gamma and IL-2 following stimulation with a pool of overlapping peptides that cover the entire N protein sequence. The N-specific IFN-gamma(+)CD4(+) T cells were mainly composed of CD45RA(-)CCR7(+)CD62L(-) cells, whereas IFN-gamma(+)CD8(+) memory T cells were mostly contained within CD45RA(+)CCR7(-)CD62L(-) cell population. Epitope mapping study indicated that a cluster of overlapping peptides located in the C-terminal region (amino acids [aa] 331 to 362) of N protein contained at least two different T-cell epitopes. The results indicated that human memory T-cell responses specific for SARS-CoV N protein could persist for 2 years in the absence of antigen, which would be a valuable for the design of effective vaccines against SARS-CoV and for basic studies of human T-cell memory.
核衣壳(N)蛋白是严重急性呼吸综合征(SARS)冠状病毒(SARS-CoV)的一种结构成分,在感染期间可诱导SARS患者产生抗体反应。然而,尚不清楚SARS-CoV N蛋白是否能在人体内诱导记忆性T细胞反应长期持续存在。在本研究中,我们发现,用覆盖整个N蛋白序列的重叠肽池刺激后,完全康复的SARS患者的外周血单个核细胞(PBMC)迅速产生γ干扰素和白细胞介素-2。N特异性γ干扰素(+)CD4(+)T细胞主要由CD45RA(-)CCR7(+)CD62L(-)细胞组成,而γ干扰素(+)CD8(+)记忆性T细胞大多包含在CD45RA(+)CCR7(-)CD62L(-)细胞群体中。表位作图研究表明,位于N蛋白C末端区域(氨基酸[aa]331至362)的一组重叠肽包含至少两个不同的T细胞表位。结果表明,在没有抗原的情况下,针对SARS-CoV N蛋白的人类记忆性T细胞反应可持续2年,这对于设计有效的抗SARS-CoV疫苗以及人类T细胞记忆的基础研究具有重要价值。