Persistent memory CD4+ (and CD8+ T-cell responses in recovered severe acute respiratory syndrome (SARS) patients to SARS coronavirus M antigen

The membrane (M) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) is a major glycoprotein with multiple biological functions. In this study, we found that memory T cells against M protein were persistent in recovered SARS patients by detecting gamma interferon (IFN-gamma) production using ELISA and ELISpot assays. Flow cytometric analysis showed that both CD4(+) and CD8(+) T cells were involved in cellular responses to SARS-CoV IM antigen. Furthermore, memory CD8+ T cells displayed an effector memory cell phenotype expressing CD45RO(-) CCR7(-) CD62L(-). In contrast, the majority of IFN-gamma(+) CD4(+) T cells were central memory cells with the expression of CD45RO(+) CCR7(+) CD62L(-). The epitope screening from 30 synthetic overlapping peptides that cover the entire SARS-CoV IM protein identified four human T-cell immunodominant pepticles, p21-44, p65-91, p117-140 and p200-220. All four immunodominant pepticles could elicit cellular immunity with a predominance of CD8+ T-cell response. This data may have important implication for developing SARS vaccines.