Identification of an HLA-A*0201-restricted CD8+ T-cell epitope SSp-1 of SARS-CoV spike protein.
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.
Wang
Baomei
B
Institute of Immunology, Second Military Medical University, Shanghai, People's Republic of China.
Chen
Huabiao
H
Jiang
Xiaodong
X
Zhang
Minghui
M
Wan
Tao
T
Li
Nan
N
Zhou
Xiangyang
X
Wu
Yanfeng
Y
Yang
Feng
F
Yu
Yizhi
Y
Wang
Xiaoning
X
Yang
Ruifu
R
Cao
Xuetao
X
D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015234:HLA-A Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015789:HLA-A2 Antigen; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D045473:Severe acute respiratory syndrome-related coronavirus / Q000737:chemistry / Q000276:immunology*; D064370:Spike Glycoprotein, Coronavirus; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D014161:Transduction, Genetic; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D015678:Viral Structural Proteins / Q000235:genetics / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; D015678:Viral Structural Proteins; C578557:spike glycoprotein, SARS-CoV; C578553:spike protein, mouse hepatitis virus; D007371:Interferon-gamma