title: Long-term adaptation of the influenza A virus by escaping cytotoxic T-cell recognition.
abstract: The evolutionary adaptation of the influenza A virus (IAV) to human antibodies is well characterised. Much less is known about the long-term evolution of cytotoxic T lymphocyte (CTL) epitopes, which are important antigens for clearance of infection. We construct an antigenic map of IAVs of all human subtypes using a compendium of 142 confirmed CTL epitopes, and show that IAV evolved gradually in the period 1932-2015, with infrequent antigenic jumps in the H3N2 subtype. Intriguingly, the number of CTL epitopes per virus decreases with more than one epitope per three years in the H3N2 subtype (from 84 epitopes per virus in 1968 to 64 in 2015), mostly attributed to the loss of HLA-B epitopes. We confirm these observations with epitope predictions. Our findings indicate that selection pressures imposed by CTL immunity shape the long-term evolution of IAV.
authors.affiliation: Theoretical Biology, Utrecht University, Utrecht, The Netherlands.|National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
authors.forename: Rutger G
authors.initials: RG
authors.lastname: Woolthuis
authors.affiliation: Theoretical Biology, Utrecht University, Utrecht, The Netherlands.|National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
authors.forename: Christiaan H
authors.initials: CH
authors.lastname: van Dorp
authors.affiliation: Theoretical Biology, Utrecht University, Utrecht, The Netherlands.
authors.forename: Can
authors.initials: C
authors.lastname: Keşmir
authors.affiliation: Theoretical Biology, Utrecht University, Utrecht, The Netherlands.
authors.forename: Rob J
authors.initials: RJ
authors.lastname: de Boer
authors.affiliation: National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
authors.forename: Michiel
authors.initials: M
authors.lastname: van Boven
mesh_terms: D018984:Epitopes, T-Lymphocyte / Q000235:genetics* / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics* / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D015235:HLA-B Antigens; D016056:Immunodominant Epitopes