Identification of a novel conserved HLA-A*0201-restricted epitope from the spike protein of SARS-CoV

BMC Immunol. 2009 Dec 3;10:61. doi: 10.1186/1471-2172-10-61.

Abstract

Background: 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.

Results: 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-gamma and lysed target cells upon stimulation with Sp8 peptide-pulsed autologous dendritic cells in comparison to other candidates.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Conserved Sequence
  • Coronavirus / immunology*
  • Cytotoxicity, Immunologic
  • Epitope Mapping
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology
  • Epitopes, T-Lymphocyte / metabolism*
  • HLA-A Antigens / genetics
  • HLA-A Antigens / immunology
  • HLA-A Antigens / metabolism*
  • HLA-A2 Antigen
  • Humans
  • Immunization
  • Interferon-gamma / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Transgenic
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism*
  • Protein Binding
  • Severe Acute Respiratory Syndrome / immunology
  • Spike Glycoprotein, Coronavirus
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism*
  • T-Lymphocytes, Cytotoxic / pathology
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology
  • Viral Envelope Proteins / metabolism*

Substances

  • Epitopes, T-Lymphocyte
  • HLA-A Antigens
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • Membrane Glycoproteins
  • Peptide Fragments
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins
  • spike glycoprotein, SARS-CoV
  • spike protein, mouse hepatitis virus
  • Interferon-gamma