ArticleJournal of immunology (Baltimore, Md. : 1950)2011
Translation of HLA-HIV associations to the cellular level: HIV adapts to inflate CD8 T cell responses against Nef and HLA-adapted variant epitopes.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 27 citations in OpenAlex.
- High frequency of HIV mutations associated with HLA-C suggests enhanced HLA-C-restricted CTL selective pressure associated with an AIDS-protective polymorphism.Journal of immunology (Baltimore, Md. : 1950) · 2012Trial
- Co-evolved Partners of Immunity: A Trait-Based Map of Human Keystone Organisms.bioRxiv : the preprint server for biology · 2026Article
- Keystone Epitope Theory: An Ecological Perspective on RNA Viruses, Tumor Immunoediting, and Vaccine Design.Pathogens & immunity · 2026Review
- HIV-1 adapts to HLA class II-associated selection pressure exerted by CD4Science advances · 2025Article
- Adaptation to HLA-associated immune pressure over the course of HIV infection and in circulating HIV-1 strains.PLoS pathogens · 2022Article
- Cross-Reactivity to Mutated Viral Immune Targets Can Influence CD8Frontiers in immunology · 2021Article
- Deep sequence analysis of HIV adaptation following vertical transmission reveals the impact of immune pressure on the evolution of HIV.PLoS pathogens · 2019Article
- Evidence of CD4Scientific reports · 2018Article
- Weaker HLA Footprints on HIV in the Unique and Highly Genetically Admixed Host Population of Mexico.Journal of virology · 2018Article
- HLA-DQB1*06 and breadth of Nef core region-specific T-cell response are associated with slow disease progression in antiretroviral therapy-naive Chinese HIV-1 subtype B patients.Human vaccines & immunotherapeutics · 2017Article
- Impact of pre-adapted HIV transmission.Nature medicine · 2016Article
- Enhanced Recognition of HIV-1 Cryptic Epitopes Restricted by HLA Class I Alleles Associated With a Favorable Clinical Outcome.Journal of acquired immune deficiency syndromes (1999) · 2015Article
- HLA Class-II Associated HIV Polymorphisms Predict Escape from CD4+ T Cell Responses.PLoS pathogens · 2015Article
- Viremic control and viral coreceptor usage in two HIV-1-infected persons homozygous for CCR5 Δ32.AIDS (London, England) · 2015Article
- Linking pig-tailed macaque major histocompatibility complex class I haplotypes and cytotoxic T lymphocyte escape mutations in simian immunodeficiency virus infection.Journal of virology · 2014Article
- Comparison of experimental fine-mapping to in silico prediction results of HIV-1 epitopes reveals ongoing need for mapping experiments.Immunology · 2014Article
- Host genetics and viral load in primary HIV-1 infection: clear evidence for gene by sex interactions.Human genetics · 2014Article
- Positioning of APOBEC3G/F mutational hotspots in the human immunodeficiency virus genome favors reduced recognition by CD8+ T cells.PloS one · 2014Article
- Article
- HIV escape mutations occur preferentially at HLA-binding sites of CD8 T-cell epitopes.AIDS (London, England) · 2013Article
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
Strong statistical associations between polymorphisms in HIV-1 population sequences and carriage of HLA class I alleles have been widely used to identify possible sites of CD8 T cell immune selection in vivo. However, there have been few attempts to prospectively and systematically test these genetic hypotheses arising from population-based studies at a cellular, functional level. We assayed CD8 T cell epitope-specific IFN-γ responses in 290 individuals from the same cohort, which gave rise to 874 HLA-HIV associations in genetic analyses, taking into account autologous viral sequences and individual HLA genotypes. We found immunological evidence for 58% of 374 associations tested as sites of primary immune selection and identified up to 50 novel HIV-1 epitopes using this reverse-genomics approach. Many HLA-adapted epitopes elicited equivalent or higher-magnitude IFN-γ responses than did the nonadapted epitopes, particularly in Nef. At a population level, inclusion of all of the immunoreactive variant CD8 T cell epitopes in Gag, Pol, Nef, and Env suggested that HIV adaptation leads to an inflation of Nef-directed immune responses relative to other proteins. We concluded that HLA-HIV associations mark viral epitopes subject to CD8 T cell selection. These results can be used to guide functional studies of specific epitopes and escape mutations, as well as to test, train, and evaluate analytical models of viral escape and fitness. The inflation of Nef and HLA-adapted variant responses may have negative effects on natural and vaccine immunity against HIV and, therefore, has implications for diversity coverage approaches in HIV vaccine design.
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