tetano
Editor, Senior Moderator
PLoS One. 2010 May 11;5(5):e10583.
Significant Impact of Sequence Variations in the Nucleoprotein on CD8 T Cell-Mediated Cross-Protection against Influenza A Virus Infections.
Zhong W, Liu F, Dong L, Lu X, Hancock K, Reinherz EL, Katz JM, Sambhara S.
Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
Abstract
BACKGROUND: Memory CD8 T cells to influenza A viruses are widely detectable in healthy human subjects and broadly cross-reactive for serologically distinct influenza A virus subtypes. However, it is not clear to what extent such pre-existing cellular immunity can provide cross-subtype protection against novel emerging influenza A viruses. METHODOLOGY/PRINCIPAL FINDINGS: We show in the mouse model that naturally occurring sequence variations of the conserved nucleoprotein of the virus significantly impact cross-protection against lethal disease in vivo. When priming and challenge viruses shared identical sequences of the immunodominant, protective NP(366)/D(b) epitope, strong cross-subtype protection was observed. However, when they did not share complete sequence identity in this epitope, cross-protection was considerably reduced. Contributions of virus-specific antibodies appeared to be minimal under these circumstances. Detailed analysis revealed that the magnitude of the memory CD8 T cell response triggered by the NP(366)/D(b) variants was significantly lower than those triggered by the homologous NP(366)/D(b) ligand. It appears that strict specificity of a dominant public TCR to the original NP(366)/D(b) ligand may limit the expansion of cross-reactive memory CD8 T cells to the NP(366)/D(b) variants. CONCLUSIONS/SIGNIFICANCE: Pre-existing CD8 T cell immunity may provide substantial cross-protection against heterosubtypic influenza A viruses, provided that the priming and the subsequent challenge viruses share the identical sequences of the immunodominant, protective CTL epitopes.
PMID: 20485501 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/20485501?dopt=Abstract
Significant Impact of Sequence Variations in the Nucleoprotein on CD8 T Cell-Mediated Cross-Protection against Influenza A Virus Infections.
Zhong W, Liu F, Dong L, Lu X, Hancock K, Reinherz EL, Katz JM, Sambhara S.
Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
Abstract
BACKGROUND: Memory CD8 T cells to influenza A viruses are widely detectable in healthy human subjects and broadly cross-reactive for serologically distinct influenza A virus subtypes. However, it is not clear to what extent such pre-existing cellular immunity can provide cross-subtype protection against novel emerging influenza A viruses. METHODOLOGY/PRINCIPAL FINDINGS: We show in the mouse model that naturally occurring sequence variations of the conserved nucleoprotein of the virus significantly impact cross-protection against lethal disease in vivo. When priming and challenge viruses shared identical sequences of the immunodominant, protective NP(366)/D(b) epitope, strong cross-subtype protection was observed. However, when they did not share complete sequence identity in this epitope, cross-protection was considerably reduced. Contributions of virus-specific antibodies appeared to be minimal under these circumstances. Detailed analysis revealed that the magnitude of the memory CD8 T cell response triggered by the NP(366)/D(b) variants was significantly lower than those triggered by the homologous NP(366)/D(b) ligand. It appears that strict specificity of a dominant public TCR to the original NP(366)/D(b) ligand may limit the expansion of cross-reactive memory CD8 T cells to the NP(366)/D(b) variants. CONCLUSIONS/SIGNIFICANCE: Pre-existing CD8 T cell immunity may provide substantial cross-protection against heterosubtypic influenza A viruses, provided that the priming and the subsequent challenge viruses share the identical sequences of the immunodominant, protective CTL epitopes.
PMID: 20485501 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/20485501?dopt=Abstract