Identification of a novel conserved HLA-A*0201-restricted epitope from the spike protein of SARS-CoV
Institute of Immunology, PLA, Third Military Medical University, 30 Gaotanyan Street, Chongqing 400038, PR China
BMC Immunology 2009, 10:61 doi:10.1186/1471-2172-10-61Published: 3 December 2009
The spike (S) protein is a major structural glycoprotein of coronavirus (CoV), the causal agent of severe acute respiratory syndrome (SARS). The S protein is a potent target for SARS-specific cell-mediated immune responses. However, the mechanism CoV pathogenesis in SARS and the role of special CTLs in virus clearance are still largely uncharacterized. Here, we describe a study that leads to the identification of a novel HLA-A*0201-restricted epitope from conserved regions of S protein.
First, different SARS-CoV sequences were analyzed to predict eight candidate peptides from conserved regions of the S protein based upon HLA-A*0201 binding and proteosomal cleavage. Four of eight candidate peptides were tested by HLA-A*0201 binding assays. Among the four candidate peptides, Sp8 (S958-966, VLNDILSRL) induced specific CTLs both ex vivo in PBLs of healthy HLA-A2+ donors and in HLA-A2.1/Kb transgenic mice immunized with a plasmid encoding full-length S protein. The immunized mice released IFN-γ and lysed target cells upon stimulation with Sp8 peptide-pulsed autologous dendritic cells in comparison to other candidates.
These results suggest that Sp8 is a naturally processed epitope. We propose that Sp8 epitope should help in the characterization of mechanisms of virus control and immunopathology in SARS-CoV infection.