Epitopes described in "Significant impact of sequence variations in the nucleoprotein on CD8 T cell-mediated cross-protection against influenza A virus infections."

Article Authors:Weimin Zhong; Feng Liu; Libo Dong; Xiuhua Lu; Kathy Hancock; Ellis L Reinherz; Jacqueline M Katz; Suryaprakash Sambhara
Article Title:Significant impact of sequence variations in the nucleoprotein on CD8 T cell-mediated cross-protection against influenza A virus infections.
Reference Detail
Reference ID:1019789
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.
Affiliations:Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America. wzhong@cdc.gov.
Reference Type:Literature
PubMed ID:20485501
Journal:PLoS One
Journal Volume:5
Article Pages:e10583
Journal ISSN:1932-6203
Article Chemical List:Antibodies, Viral;Epitopes;Nucleoproteins;Receptors, Antigen, T-Cell;Viral Proteins
Article MeSH List:Amino Acid Sequence; Animals; Antibodies, Viral(immunology); CD8-Positive T-Lymphocytes(immunology; virology); Cross Protection(immunology); Cross-Priming(immunology); Epitopes(chemistry; immunology); Female; Genetic Variation; Humans; Immunity(immunology); Immunologic Memory; Influenza A virus(classification; immunology); Influenza, Human(blood; immunology; virology); Lymphocyte Subsets(immunology; virology); Mice; Molecular Sequence Data; Mucous Membrane(immunology); Nucleoproteins(chemistry; immunology); Orthomyxoviridae Infections(blood; immunology; virology); Receptors, Antigen, T-Cell(immunology); T-Lymphocytes, Cytotoxic(immunology; virology); Viral Proteins(chemistry; immunology)
Curation Last Updated:2015-07-30 20:36:25