title: Vertical T cell immunodominance and epitope entropy determine HIV-1 escape.
abstract: HIV-1 accumulates mutations in and around reactive epitopes to escape recognition and killing by CD8+ T cells. Measurements of HIV-1 time to escape should therefore provide information on which parameters are most important for T cell-mediated in vivo control of HIV-1. Primary HIV-1-specific T cell responses were fully mapped in 17 individuals, and the time to virus escape, which ranged from days to years, was measured for each epitope. While higher magnitude of an individual T cell response was associated with more rapid escape, the most significant T cell measure was its relative immunodominance measured in acute infection. This identified subject-level or "vertical" immunodominance as the primary determinant of in vivo CD8+ T cell pressure in HIV-1 infection. Conversely, escape was slowed significantly by lower population variability, or entropy, of the epitope targeted. Immunodominance and epitope entropy combined to explain half of all the variability in time to escape. These data explain how CD8+ T cells can exert significant and sustained HIV-1 pressure even when escape is very slow and that within an individual, the impacts of other T cell factors on HIV-1 escape should be considered in the context of immunodominance.
authors.affiliation: Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Michael K P
authors.initials: MK
authors.lastname: Liu
authors.forename: Natalie
authors.initials: N
authors.lastname: Hawkins
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Ritchie
authors.forename: Vitaly V
authors.initials: VV
authors.lastname: Ganusov
authors.forename: Victoria
authors.initials: V
authors.lastname: Whale
authors.forename: Simon
authors.initials: S
authors.lastname: Brackenridge
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Pavlicek
authors.forename: Fangping
authors.initials: F
authors.lastname: Cai
authors.forename: Melissa
authors.initials: M
authors.lastname: Rose-Abrahams
authors.forename: Florette
authors.initials: F
authors.lastname: Treurnicht
authors.forename: Peter
authors.initials: P
authors.lastname: Hraber
authors.forename: Catherine
authors.initials: C
authors.lastname: Riou
authors.forename: Clive
authors.initials: C
authors.lastname: Gray
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.forename: Rachel
authors.initials: R
authors.lastname: Tanner
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Ping
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Anderson
authors.forename: Ronald
authors.initials: R
authors.lastname: Swanstrom
authors.forename: Myron
authors.initials: M
authors.lastname: Cohen
authors.forename: Salim S Abdool
authors.initials: SS
authors.lastname: Karim
authors.forename: Barton
authors.initials: B
authors.lastname: Haynes
authors.forename: Persephone
authors.initials: P
authors.lastname: Borrow
authors.forename: Alan S
authors.initials: AS
authors.lastname: Perelson
authors.forename: George M
authors.initials: GM
authors.lastname: Shaw
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
authors.forename: Carolyn
authors.initials: C
authors.lastname: Williamson
authors.forename: Bette T
authors.initials: BT
authors.lastname: Korber
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Steve
authors.initials: S
authors.lastname: Self
authors.forename: Andrew
authors.initials: A
authors.lastname: McMichael
authors.forename: Nilu
authors.initials: N
authors.lastname: Goonetilleke
mesh_terms: D000293:Adolescent; D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D057131:Immune Evasion; D007111:Immunity, Cellular; D008297:Male
chemical_list: D018984:Epitopes, T-Lymphocyte