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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.


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IMMUNOBIOLOGY

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

From the Institute of Immunology, Second Military Medical University, Shanghai, People's Republic of China; the Institute of Immunology, Zhejiang University, Hangzhou, People's Republic of China; the Institute of Molecular Immunology, First Military Medical University, Guangzhou, People's Republic of China; and the Institute of Microbiology and Epidemiology, Chinese Academy of Military Medical Sciences, Beijing, People's Republic of China.

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. SARS-CoV protein-derived peptide-1 (SSp-1 RLNEVAKNL), 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 major histocompatibility complex (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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