Peng Hui, Yang Li-tao, Li Jian, Lu Zhi-qiang, Wang Ling-yun, 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.
Microbes Infect. 2006 Aug;8(9-10):2424-31. doi: 10.1016/j.micinf.2006.05.008. Epub 2006 Jun 30.
E protein is a membrane component of severe acute respiratory syndrome coronavirus (SARS-CoV). Disruption of E protein may reduce viral infectivity. Thus, the SARS-CoV E protein is considered a potential target for the development of antiviral drugs. However, the cellular immune responses to E protein remain unclear in humans. 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 9 peptides overlapping the entire E protein sequence. Analysis of the immune responses by flow cytometry showed that both CD4+ and CD8+T cells were involved in the SARS-CoV E-specific immune responses after stimulation with SARS-CoV E peptides. Moreover, the majority of IFN-gamma+CD4+T cells were central memory cells expressing CD45RO+CCR7+CD62L-; whereas IFN-gamma+CD8+ memory T cells were mostly effector memory cells expressing CD45RO-CCR7-CD62L-. The results of T-cell responses to 9 individual peptides indicated that the E protein contained at least two major T cell epitopes (E2 amino acid [aa] 9-26 and E5-6: aa 33-57) which were important in eliciting cellular immune response to SARS-CoV E protein in humans.
E蛋白是严重急性呼吸综合征冠状病毒(SARS-CoV)的膜成分。E蛋白的破坏可能会降低病毒的感染性。因此,SARS-CoV E蛋白被认为是开发抗病毒药物的潜在靶点。然而,人类对E蛋白的细胞免疫反应仍不清楚。在本研究中,我们发现,来自已完全康复的SARS患者的外周血单个核细胞(PBMC)在用覆盖整个E蛋白序列的9种肽段混合物刺激后,迅速产生γ干扰素和白细胞介素-2。通过流式细胞术分析免疫反应表明,在用SARS-CoV E肽段刺激后,CD4+和CD8+T细胞均参与了SARS-CoV E特异性免疫反应。此外,大多数γ干扰素+CD4+T细胞是表达CD45RO+CCR7+CD62L-的中枢记忆细胞;而γ干扰素+CD8+记忆T细胞大多是表达CD45RO-CCR7-CD62L-的效应记忆细胞。对9种单个肽段的T细胞反应结果表明,E蛋白至少包含两个主要的T细胞表位(E2氨基酸[aa]9-26和E5-6:aa 33-57),它们在引发人类对SARS-CoV E蛋白的细胞免疫反应中起重要作用。