HLA-A*0201 T-cell epitopes in severe acute respiratory syndrome (SARS) coronavirus nucleocapsid and spike proteins
- Department of Microbiology and Immunology, National Defense Medical Center, Taipei 114, Taiwan (China)
- Institute of Preventive Medicine, National Defense Medical Center, Taipei 114, Taiwan (China)
- Vaccine Research and Development Center, National Health Research Institutes, Taipei 115, Taiwan (China)
- Department of Medical Research, Mackay Memorial Hospital, Taipei 104, Taiwan (China)
- Department of Microbiology and Immunology, National Defense Medical Center, Taipei 114, Taiwan (China) and Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan (China)
The immunogenicity of HLA-A*0201-restricted cytotoxic T lymphocyte (CTL) peptide in severe acute respiratory syndrome coronavirus (SARS-CoV) nuclear capsid (N) and spike (S) proteins was determined by testing the proteins' ability to elicit a specific cellular immune response after immunization of HLA-A2.1 transgenic mice and in vitro vaccination of HLA-A2.1 positive human peripheral blood mononuclearcytes (PBMCs). First, we screened SARS N and S amino acid sequences for allele-specific motif matching those in human HLA-A2.1 MHC-I molecules. From HLA peptide binding predictions (http://thr.cit.nih.gov/molbio/hla{sub b}ind/), ten each potential N- and S-specific HLA-A2.1-binding peptides were synthesized. The high affinity HLA-A2.1 peptides were validated by T2-cell stabilization assays, with immunogenicity assays revealing peptides N223-231, N227-235, and N317-325 to be First identified HLA-A*0201-restricted CTL epitopes of SARS-CoV N protein. In addition, previous reports identified three HLA-A*0201-restricted CTL epitopes of S protein (S978-986, S1203-1211, and S1167-1175), here we found two novel peptides S787-795 and S1042-1050 as S-specific CTL epitopes. Moreover, our identified N317-325 and S1042-1050 CTL epitopes could induce recall responses when IFN-{gamma} stimulation of blood CD8{sup +} T-cells revealed significant difference between normal healthy donors and SARS-recovered patients after those PBMCs were in vitro vaccinated with their cognate antigen. Our results would provide a new insight into the development of therapeutic vaccine in SARS.
- OSTI ID:
- 20798961
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 344, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2006.03.152; PII: S0006-291X(06)00690-5; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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