title: Fitness costs limit escape from cytotoxic T lymphocytes by influenza A viruses.
abstract: The use of cytotoxic T lymphocyte (CTL)-inducing vaccines could afford both homo- and heterosubtypic immunity. However, amino acid variation in CTL epitopes associated with escape from CTL-mediated immunity might undermine the use of these vaccines. To assess the impact of amino acid substitutions in highly conserved epitopes on viral fitness and recognition by specific CTL, we performed a mutational analysis of various CTL epitopes. Our findings indicated that fitness costs limited variation in functionally constrained epitopes, especially at anchor residues.
authors.affiliation: Department of Virology and WHO National Influenza Center, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.
authors.forename: E G M
authors.initials: EG
authors.lastname: Berkhoff
authors.forename: E
authors.initials: E
authors.lastname: de Wit
authors.forename: M M
authors.initials: MM
authors.lastname: Geelhoed-Mieras
authors.forename: A C M
authors.initials: AC
authors.lastname: Boon
authors.forename: J
authors.initials: J
authors.lastname: Symons
authors.forename: R A M
authors.initials: RA
authors.lastname: Fouchier
authors.forename: A D M E
authors.initials: AD
authors.lastname: Osterhaus
authors.forename: G F
authors.initials: GF
authors.lastname: Rimmelzwaan
mesh_terms: D000595:Amino Acid Sequence; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D016601:RNA-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D016601:RNA-Binding Proteins