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International Immunology Advance Access originally published online on December 2, 2008
International Immunology 2009 21(1):63-71; doi:10.1093/intimm/dxn124
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© The Japanese Society for Immunology. 2008. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Searching immunodominant epitopes prior to epidemic: HLA class II-restricted SARS-CoV spike protein epitopes in unexposed individuals

Junbao Yang1, Eddie James1, Michelle Roti1, Laurie Huston1, John A. Gebe1 and William W. Kwok1,2

1 Benaroya Research Institute at Virginia Mason, Seattle, WA, USA
2 Department of Immunology, University of Washington, Seattle, WA, USA

Correspondence to: W. W. Kwok; E-mail: bkwok{at}benaroyaresearch.org

Identification of dominant T cell epitopes within newly emerging and re-emerging infectious organisms is valuable in understanding pathogenic immune responses and potential vaccine designs. However, difficulties in obtaining samples from patients or convalescent subjects have hampered research in this direction. We demonstrated a strategy, tetramer-guided epitope mapping, that specific CD4+ T cell epitopes can be identified by using PBMC from subjects that have not been exposed to the infectious organism. Sixteen HLA-DR0401- and 14 HLA-DR0701-restricted epitopes within spike protein of severe acute respiratory syndrome-coronavirus (SARS-CoV) were identified. Among these, spike protein residues 159–171, 166–178, 449–461 and 1083–1097 were identified to contain naturally processed immunodominant epitopes based on strong in vitro T cell responses of PBMC (as assayed by tetramer staining) to intact spike protein stimulation. These immunodominant epitopes were confirmed in vivo in HLA-DR0401 transgenic mice by immunizing with spike protein. Furthermore, the epitope-specific T cells from naive donors secreted IFN-{gamma} and IL-13 upon re-stimulation with corresponding tetramers. Our study demonstrates a strategy to determine potential immunodominant epitopes for emerging infectious pathogens prior to their epidemic circulation.

Keywords: MHC class II tetramer, tetramer-guided epitope mapping

Transmitting editor: Anne Cooke

Received 17 July 2008, accepted 4 November 2008.


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