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Blood, 1 July 2004, Vol. 104, No. 1, pp. 200-206.
Prepublished online as a Blood First Edition Paper on March 11, 2004; DOI 10.1182/blood-2003-11-4072.
 Previous Article | Next Article 
Submitted December 1, 2003
Accepted February 27, 2004
Identification of an HLA-A*0201-restricted CD8+ T-cell epitope SSp-1 of SARS-CoV spike protein
Baomei Wang, Huabiao Chen, Xiaodong Jiang, Minghui Zhang, Tao Wan, Nan Li, Xiangyang Zhou, Yanfeng Wu, Feng Yang, Yizhi Yu, Xiaoning Wang, Ruifu Yang, and Xuetao Cao*
Institute of Immunology, Second Military Medical University, Shanghai, China
Institute of Immunology, Zhejiang University, Hangzhou, Zhejiang, China
Institute of Molecular Immunology, First Military Medical University, Guangzhou, Guangdong, China
Institute of Microbiology and Epidemiology, Chinese Academy of Military Medical Sciences, Beijing, China
Institute of Immunology, Second Military Medical University, Shanghai, China; Institute of Immunology, Zhejiang University, Hangzhou, Zhejiang, China
* Corresponding author; email: caoxt{at}public3.sta.net.cn.
A novel coronavirus, severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV), has been identified as the causal agent of SARS. Spike (S) protein is a major structural glycoprotein of the SARS virus, and a potential target for SARS-specific cell-mediated immune responses. A panel of S protein-derived peptides was tested for their binding affinity to HLA-A*0201 molecules. Peptides with high affinity for HLA-A*0201 were then assessed for their capacity to elicit specific immune responses mediated by cytotoxic T lymphocytes (CTLs) both in vivo, in HLA-A2.1/Kb transgenic mice, and in vitro, from peripheral blood lymphocytes (PBLs) sourced from healthy HLA-A2.1+ donors. One of the tested peptides, SSp-1, induced peptide-specific CTLs both in vivo (transgenic mice) and in vitro (human PBLs) which specifically released interferon-gamma (IFN-gamma) upon stimulation with SSp-1-pulsed autologous dendritic cells (DCs) or T2 cells. SSp-1-specific CTLs also lysed MHC-matched tumor cell lines engineered to express S proteins. HLA-A*0201-SSp-1 tetramer staining revealed the presence of significant populations of SSp-1-specific CTLs in SSp-1-induced CD8+ T cells. We propose that the newly identified epitope SSp-1 will help in the characterization of virus control mechanisms and immunopathology in SARS-CoV infection, and may be relevant to the development of immunotherapeutic approaches for SARS.
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