ArticlePLoS pathogens2011
The antiviral efficacy of HIV-specific CD8⁺ T-cells to a conserved epitope is heavily dependent on the infecting HIV-1 isolate.
Article in PLoS pathogens, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- Epistatic interaction between ERAP2 and HLA modulates HIV-1 adaptation and disease outcome in an Australian population.PLoS pathogens · 2024Article
- The molecular mechanisms of CD8Frontiers in immunology · 2024Review
- Article
- T cells are ready for the fight against monkeypox.Cell host & microbe · 2022Article
- A longitudinal analysis of immune escapes from HLA-B*13-restricted T-cell responses at early stage of CRF01_AE subtype HIV-1 infection and implications for vaccine design.BMC immunology · 2022Article
- An immunodominant NPNature immunology · 2022Article
- HIV-1-Specific Immunodominant T-Cell Responses Drive the Dynamics of HIV-1 Recombination Following Superinfection.Frontiers in immunology · 2021Article
- Antigen processing and presentation in HIV infection.Molecular immunology · 2019Review
- High polymorphism rates in well-known T cell epitopes restricted by protective HLA alleles during HIV infection are associated with rapid disease progression in early-infected MSM in China.Medical microbiology and immunology · 2019Article
- APOBEC3G Regulation of the Evolutionary Race Between Adaptive Immunity and Viral Immune Escape Is Deeply Imprinted in the HIV Genome.Frontiers in immunology · 2018Article
- Multi-layered Gag-specific immunodominant responses contribute to improved viral control in the CRF01_AE subtype of HIV-1-infected MSM subjects.BMC immunology · 2016Article
- The presence of prolines in the flanking region of an immunodominant HIV-2 gag epitope influences the quality and quantity of the epitope generated.European journal of immunology · 2015Article
- Multilayered HIV-1 gag-specific T-cell responses contribute to slow progression in HLA-A*30-B*13-C*06-positive patients.AIDS (London, England) · 2015Article
- Variable processing and cross-presentation of HIV by dendritic cells and macrophages shapes CTL immunodominance and immune escape.PLoS pathogens · 2015Article
- HIV-1 adaptation to antigen processing results in population-level immune evasion and affects subtype diversification.Cell reports · 2014Article
- HLA-B may be more protective against HIV-1 than HLA-A because it resists negative regulatory factor (Nef) mediated down-regulation.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Development of a novel in silico docking simulation model for the fine HIV-1 cytotoxic T lymphocyte epitope mapping.PloS one · 2012Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
A major challenge to developing a successful HIV vaccine is the vast diversity of viral sequences, yet it is generally assumed that an epitope conserved between different strains will be recognised by responding T-cells. We examined whether an invariant HLA-B8 restricted Nef₉₀₋₉₇ epitope FL8 shared between five high titre viruses and eight recombinant vaccinia viruses expressing Nef from different viral isolates (clades A-H) could activate antiviral activity in FL8-specific cytotoxic T-lymphocytes (CTL). Surprisingly, despite epitope conservation, we found that CTL antiviral efficacy is dependent on the infecting viral isolate. Only 23% of Nef proteins, expressed by HIV-1 isolates or as recombinant vaccinia-Nef, were optimally recognised by CTL. Recognition of the HIV-1 isolates by CTL was independent of clade-grouping but correlated with virus-specific polymorphisms in the epitope flanking region, which altered immunoproteasomal cleavage resulting in enhanced or impaired epitope generation. The finding that the majority of virus isolates failed to present this conserved epitope highlights the importance of viral variance in CTL epitope flanking regions on the efficiency of antigen processing, which has been considerably underestimated previously. This has important implications for future vaccine design strategies since efficient presentation of conserved viral epitopes is necessary to promote enhanced anti-viral immune responses.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.