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Pubmed ID :23221345
Publication Date : //

Vertical T cell immunodominance and epitope entropy determine HIV-1 escape.


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 : Liu Michael K P , Hawkins Natalie , Ritchie Adam J , Ganusov Vitaly V , Whale Victoria , Brackenridge Simon , Li Hui , Pavlicek Jeffrey W , Cai Fangping , Rose-Abrahams Melissa , Treurnicht Florette , Hraber Peter , Riou Catherine , Gray Clive , Ferrari Guido , Tanner Rachel , Ping Li-Hua , Anderson Jeffrey A , Swanstrom Ronald , , Cohen Myron , Karim Salim S Abdool , Haynes Barton , Borrow Persephone , Perelson Alan S , Shaw George M , Hahn Beatrice H , Williamson Carolyn , Korber Bette T , Gao Feng , Self Steve , McMichael Andrew , Goonetilleke Nilu ,

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