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

Authors
  • Wang, Baomei1
  • Chen, Huabiao
  • Jiang, Xiaodong
  • Zhang, Minghui
  • Wan, Tao
  • Li, Nan
  • Zhou, Xiangyang
  • Wu, Yanfeng
  • Yang, Feng
  • Yu, Yizhi
  • Wang, Xiaoning
  • Yang, Ruifu
  • Cao, Xuetao
  • 1 Institute of Immunology, Second Military Medical University, Shanghai, People's Republic of China. , (China)
Type
Published Article
Journal
Blood
Publisher
American Society of Hematology
Publication Date
Jul 01, 2004
Volume
104
Issue
1
Pages
200–206
Identifiers
PMID: 15016646
Source
Medline
Language
English
License
Unknown

Abstract

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) harvested 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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