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

Publication ,  Journal Article
Liu, MKP; Hawkins, N; Ritchie, AJ; Ganusov, VV; Whale, V; Brackenridge, S; Li, H; Pavlicek, JW; Cai, F; Rose-Abrahams, M; Treurnicht, F ...
Published in: J Clin Invest
January 2013

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.

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Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

January 2013

Volume

123

Issue

1

Start / End Page

380 / 393

Location

United States

Related Subject Headings

  • Male
  • Immunology
  • Immunity, Cellular
  • Immune Evasion
  • Humans
  • HIV-1
  • HIV Infections
  • Female
  • Epitopes, T-Lymphocyte
  • CD8-Positive T-Lymphocytes
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Liu, M. K. P., Hawkins, N., Ritchie, A. J., Ganusov, V. V., Whale, V., Brackenridge, S., … Goonetilleke, N. (2013). Vertical T cell immunodominance and epitope entropy determine HIV-1 escape. J Clin Invest, 123(1), 380–393. https://doi.org/10.1172/JCI65330
Liu, Michael K. P., Natalie Hawkins, Adam J. Ritchie, Vitaly V. Ganusov, Victoria Whale, Simon Brackenridge, Hui Li, et al. “Vertical T cell immunodominance and epitope entropy determine HIV-1 escape.J Clin Invest 123, no. 1 (January 2013): 380–93. https://doi.org/10.1172/JCI65330.
Liu MKP, Hawkins N, Ritchie AJ, Ganusov VV, Whale V, Brackenridge S, et al. Vertical T cell immunodominance and epitope entropy determine HIV-1 escape. J Clin Invest. 2013 Jan;123(1):380–93.
Liu, Michael K. P., et al. “Vertical T cell immunodominance and epitope entropy determine HIV-1 escape.J Clin Invest, vol. 123, no. 1, Jan. 2013, pp. 380–93. Pubmed, doi:10.1172/JCI65330.
Liu MKP, Hawkins N, Ritchie AJ, Ganusov VV, Whale V, Brackenridge S, Li H, Pavlicek JW, Cai F, Rose-Abrahams M, Treurnicht F, Hraber P, Riou C, Gray C, Ferrari G, Tanner R, Ping L-H, Anderson JA, Swanstrom R, CHAVI Core B, Cohen M, Karim SSA, Haynes B, Borrow P, Perelson AS, Shaw GM, Hahn BH, Williamson C, Korber BT, Gao F, Self S, McMichael A, Goonetilleke N. Vertical T cell immunodominance and epitope entropy determine HIV-1 escape. J Clin Invest. 2013 Jan;123(1):380–393.

Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

January 2013

Volume

123

Issue

1

Start / End Page

380 / 393

Location

United States

Related Subject Headings

  • Male
  • Immunology
  • Immunity, Cellular
  • Immune Evasion
  • Humans
  • HIV-1
  • HIV Infections
  • Female
  • Epitopes, T-Lymphocyte
  • CD8-Positive T-Lymphocytes