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acute respiratory syndrome coronavirus (SARS-CoV), which emerged with highly contagious and life-threatening characteristics in 2002, remains a potential risk for future outbreaks. Membrane (M) and envelope (E) proteins are major structural proteins of the SARS-CoV. The M protein has been determined as a protective antigen in humoral responses. However, its potential roles in stimulating cellular immunity remain elusive.<h4>Methods</h4>In this study, a panel of peptides derived from M and E proteins were tested by in vitro refolding, T2 cell-binding assays, and responses stimulated by cytotoxic T-lymphocyte (CTL) epitopes in HLA-A2.1/K(b) transgenic mice and human peripheral blood mononuclear cells (PBMCs).<h4>Results</h4>A nonameric epitope Mn2 and a decameric epitope Md3 derived from the M protein were identified and used for the evaluation of M protein-specific immunity. Responses stimulated by M protein-specific CTL epitopes have been found in the PBMCs of donors who had recovered from SARS infection. Additionally, the transmembrane domain of the M protein may contain a T cell epitope cluster revealed by the immunogenic and structural analysis of a panel of truncated peptides overlapping with Mn2 and Md3.<h4>Conclusions</h4>The M protein of SARS-CoV holds dominant cellular immunogenicity. This, together with previous reports of a strong humoral response against the M protein, may help to further explain the immunogenicity of SARS and serves as potential targets for SARS-CoV vaccine design.","bibjson":{"author":[{"initials":"J","lastname":"Liu","name":"Liu J"},{"initials":"Y","lastname":"Sun","name":"Sun Y"},{"initials":"J","lastname":"Qi","name":"Qi J"},{"initials":"F","lastname":"Chu","name":"Chu F"},{"initials":"H","lastname":"Wu","name":"Wu H"},{"initials":"F","lastname":"Gao","name":"Gao F"},{"initials":"T","lastname":"Li","name":"Li T"},{"initials":"J","lastname":"Yan","name":"Yan J"},{"initials":"GF","lastname":"Gao","name":"Gao GF"}],"identifier":[{"id":"10.1086/656315","type":"doi"},{"id":"20831383","type":"pubmed"}],"issue":["8"],"journal":{"iso_abbreviation":"J. Infect. 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