HLA-B*14:02-restricted Env-specific CD8+ T-cell activity has highly potent antiviral efficacy associated with immune control of HIV infection

Ellen M. Leitman*, Christian B. Willberg, Ming Han Tsai, Huabiao Chen, Søren Buus, Fabian Chen, Lynn Riddell, David Haas, Jacques Fellay, James J. Goedert, Alicja Piechocka-Trocha, Bruce D. Walker, Jeffrey Martin, Steven Deeks, Steven M. Wolinsky, Jeremy Martinson, Maureen Martin, Ying Qi, Asier Sáez-Cirión, Otto O. YangPhilippa C. Matthews, Mary Carrington, Philip J.R. Goulder

*Corresponding author for this work

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Immune control of human immunodeficiency virus type 1 (HIV) infection is typically associated with effective Gag-specific CD8+ T-cell responses. We here focus on HLA-B*14, which protects against HIV disease progression, but the immunodominant HLA-B*14-restricted anti-HIV response is Env specific (ERYLKDQQL, HLA-B*14-EL9). A subdominant HLA-B*14-restricted response targets Gag (DRYFKTLRA, HLA-B*14-DA9). Using HLA-B*14/peptide-saporin-conjugated tetramers, we show that HLA-B*14-EL9 is substantially more potent at inhibiting viral replication than HLA-B*14-DA9. HLA-B*14-EL9 also has significantly higher functional avidity (P < 0.0001) and drives stronger selection pressure on the virus than HLA-B*14-DA9. However, these differences were HLA-B*14 subtype specific, applying only to HLA-B*14:02 and not to HLA-B*14:01. Furthermore, the HLA-B*14-associated protection against HIV disease progression is significantly greater for HLA-B*14:02 than for HLA-B*14:01, consistent with the superior antiviral efficacy of the HLA-B*14-EL9 response. Thus, although Gag-specific CD8+ T-cell responses may usually have greater anti-HIV efficacy, factors independent of protein specificity, including functional avidity of individual responses, are also critically important to immune control of HIV.

Original languageEnglish (US)
Article numbere00544-17
JournalJournal of virology
Volume91
Issue number22
DOIs
StatePublished - Nov 1 2017

Keywords

  • CD8 T cells
  • HIV
  • HLA-B*14
  • Immune control

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Leitman, E. M., Willberg, C. B., Tsai, M. H., Chen, H., Buus, S., Chen, F., Riddell, L., Haas, D., Fellay, J., Goedert, J. J., Piechocka-Trocha, A., Walker, B. D., Martin, J., Deeks, S., Wolinsky, S. M., Martinson, J., Martin, M., Qi, Y., Sáez-Cirión, A., ... Goulder, P. J. R. (2017). HLA-B*14:02-restricted Env-specific CD8+ T-cell activity has highly potent antiviral efficacy associated with immune control of HIV infection. Journal of virology, 91(22), [e00544-17]. https://doi.org/10.1128/JVI.00544-17