title: T-cell epitopes in severe acute respiratory syndrome (SARS) coronavirus spike protein elicit a specific T-cell immune response in patients who recover from SARS.
abstract: The immunogenicity of HLA-A2-restricted T-cell epitopes in the S protein of the Severe acute respiratory syndrome coronavirus (SARS-CoV) and of human coronavirus strain 229e (HCoV-229e) was analyzed for the elicitation of a T-cell immune response in donors who had fully recovered from SARS-CoV infection. We employed online database analysis to compare the differences in the amino acid sequences of the homologous T epitopes of HCoV-229e and SARS-CoV. The identified T-cell epitope peptides were synthesized, and their binding affinities for HLA-A2 were validated and compared in the T2 cell system. The immunogenicity of all these peptides was assessed by using T cells obtained from donors who had fully recovered from SARS-CoV infection and from healthy donors with no history of SARS-CoV infection. HLA-A2 typing by indirect immunofluorescent antibody staining showed that 51.6% of SARS-CoV-infected patients were HLA-A2 positive. Online database analysis and the T2 cell binding test disclosed that the number of HLA-A2-restricted immunogenic epitopes of the S protein of SARS-CoV was decreased or even lost in comparison with the homologous sequences of the S protein of HCoV-229e. Among the peptides used in the study, the affinity of peptides from HCoV-229e (H77 and H881) and peptides from SARS-CoV (S978 and S1203) for binding to HLA-A2 was higher than that of other sequences. The gamma interferon (IFN-gamma) release Elispot assay revealed that only SARS-CoV-specific peptides S1203 and S978 induced a high frequency of IFN-gamma-secreting T-cell response in HLA-A2(+) donors who had fully recovered from SARS-CoV infection; such a T-cell epitope-specific response was not observed in HLA-A2(+) healthy donors or in HLA-A2(-) donors who had been infected with SARS-CoV after full recovery. Thus, T-cell epitopes S1203 and S978 are immunogenic and elicit an overt specific T-cell response in HLA-A2(+) SARS-CoV-infected patients.
authors.affiliation: Department of Immunology, Peking University Health Science Centre, 38, Xueyuanlu, Beijing, 100083, People's Republic of China.
authors.forename: Yue-Dan
authors.initials: YD
authors.lastname: Wang
authors.forename: Wan-Yee Fion
authors.initials: WY
authors.lastname: Sin
authors.forename: Guo-Bing
authors.initials: GB
authors.lastname: Xu
authors.forename: Huang-Hao
authors.initials: HH
authors.lastname: Yang
authors.forename: Tin-yau
authors.initials: TY
authors.lastname: Wong
authors.forename: Xue-Wen
authors.initials: XW
authors.lastname: Pang
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: He
authors.forename: Hua-Gang
authors.initials: HG
authors.lastname: Zhang
authors.forename: Joice Na Lee
authors.initials: JN
authors.lastname: Ng
authors.forename: Chak-Sum Samuel
authors.initials: CS
authors.lastname: Cheng
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.forename: Li
authors.initials: L
authors.lastname: Meng
authors.forename: Rui-Feng
authors.initials: RF
authors.lastname: Yang
authors.forename: Sik-To
authors.initials: ST
authors.lastname: Lai
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Guo
authors.forename: Yong
authors.initials: Y
authors.lastname: Xie
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Chen
authors.forename: Huang-Hua
authors.initials: HH
authors.lastname: Yang
mesh_terms: D000595:Amino Acid Sequence; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen / Q000032:analysis; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000276:immunology*; D008969:Molecular Sequence Data; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology*; D064370:Spike Glycoprotein, Coronavirus; D013601:T-Lymphocytes / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; C578557:spike glycoprotein, SARS-CoV; C578553:spike protein, mouse hepatitis virus; D007371:Interferon-gamma