HLA-B*14: 02-restricted Env-specific CD8+ T-cell activity has highly potent antiviral efficacy associated with immune control of HIV infection
Research output: Contribution to journal › Journal article › Research › peer-review
Documents
- HLA-B*14:02-Restricted Env-Specific CD8+ T-Cell Activity Has Highly Potent Antiviral Efficacy Associated with Immune Control of HIV Infection
Final published version, 3.01 MB, PDF document
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 language | English |
---|---|
Article number | e00544-17 |
Journal | Journal of Virology |
Volume | 91 |
Issue number | 22 |
Number of pages | 19 |
ISSN | 0022-538X |
DOIs | |
Publication status | Published - Nov 2017 |
- CD8 T cells, HIV, HLA-B*14, Immune control
Research areas
Number of downloads are based on statistics from Google Scholar and www.ku.dk
ID: 186873092