Identification of an HLA-A*0201–restricted CD8(+) T-cell epitope SSp-1 of SARS-CoV spike protein

Wang, Baomei; Chen, Huabiao; Jiang, Xiaodong; Zhang, Minghui; Wan, Tao; Li, Nan; Zhou, Xiangyang; Wu, Yanfeng; Yang, Feng; Yu, Yizhi; Wang, Xiaoning; Yang, Ruifu; Cao, Xuetao

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/K(b) 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-γ (IFN-γ) 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.