Assessment of the extent of variation in influenza A virus cytotoxic T-lymphocyte epitopes by using virus-specific CD8+ T-cell clones.
The influenza A virus nucleoprotein (NP) and matrix protein are major targets for human virus-specific cytotoxic T-lymphocyte (CTL) responses. Most of the CTL epitopes that have been identified so far are conserved. However, sequence variation in CTL epitopes of the NP has recently been demonstrated to be associated with escape from virus-specific CTLs. To assess the extent of variation in CTL epitopes during influenza A virus evolution, 304 CTL clones derived from six study subjects were obtained with specificity for an influenza A/H3N2 virus isolated in 1981. Subsequently, the frequency of the CTL clones that failed to recognize a more recent influenza virus strain isolated in 2003 was determined. In four of six study subjects, CTLs were found to be specific for variable epitopes, accounting for 2.6 % of all CTL clones. For some of these CTL clones, the minimal epitope and the residues responsible for abrogation of T-cell recognition were identified.
Berkhoff
E G M
EGM
Department of Virology and Postgraduate School of Molecular Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Geelhoed-Mieras
M M
MM
Department of Virology and Postgraduate School of Molecular Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Fouchier
R A M
RAM
Department of Virology and Postgraduate School of Molecular Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Osterhaus
A D M E
ADME
Department of Virology and Postgraduate School of Molecular Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Rimmelzwaan
G F
GF
Department of Virology and Postgraduate School of Molecular Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
D000595:Amino Acid Sequence; D000940:Antigenic Variation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000235:genetics* / Q000276:immunology; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics / Q000276:immunology; D009980:Influenza A virus / Q000145:classification / Q000235:genetics / Q000276:immunology*; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000235:genetics* / Q000276:immunology; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014758:Viral Core Proteins / Q000235:genetics* / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins