ArticleAIDS (London, England)2014
Sequence variations in HIV-1 p24 Gag-derived epitopes can alter binding of KIR2DL2 to HLA-C*03:04 and modulate primary natural killer cell function.
Article in AIDS (London, England), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 45 citations in OpenAlex.
- Protein language models accurately predict polymorphic peptide-modulated NK cell receptor-HLA class I interaction strengths.Science advances · 2026Article
- HIV-1 infection of macrophages differentially primes NK-cell cytotoxicity and proinflammatory cytokine production.iScience · 2025Article
- Peptide-specific natural killer cell receptors.Oxford open immunology · 2025Review
- HLA-C Peptide Repertoires as Predictors of Clinical Response during Early SARS-CoV-2 Infection.Life (Basel, Switzerland) · 2024Article
- HIV-1 Nef-mediated downregulation of CD155 results in viral restriction by KIR2DL5+ NK cells.PLoS pathogens · 2022Article
- Host KIR/HLA-C Genotypes Determine HIV-Mediated Changes of the NK Cell Repertoire and Are Associated With Vpu Sequence Variations Impacting Downmodulation of HLA-C.Frontiers in immunology · 2022Article
- The New Kid on the Block: HLA-C, a Key Regulator of Natural Killer Cells in Viral Immunity.Cells · 2021Review
- Regulation of the human NK cell compartment by pathogens and vaccines.Clinical & translational immunology · 2021Review
- HIV-1 induced changes in HLA-C*03 : 04-presented peptide repertoires lead to reduced engagement of inhibitory natural killer cell receptors.AIDS (London, England) · 2020Article
- Primary HIV-1 Strains Use Nef To Downmodulate HLA-E Surface Expression.Journal of virology · 2019Article
- Conserved and variable natural killer cell receptors: diverse approaches to viral infections.Immunology · 2019Review
- Mutually assured destruction: the cold war between viruses and natural killer cells.Current opinion in virology · 2019Review
- HLA-C-restricted viral epitopes are associated with an escape mechanism from KIR2DL2EBioMedicine · 2019Article
- Natural killer cell specificity for viral infections.Nature immunology · 2018Review
- Specificity of inhibitory KIRs enables NK cells to detect changes in an altered peptide environment.Immunogenetics · 2018Article
- Stable Frequencies of HLA-CFrontiers in immunology · 2018Article
- Natural killer cells in HIV-1 infection and therapy.AIDS (London, England) · 2017Review
- Missing or altered self: human NK cell receptors that recognize HLA-C.Immunogenetics · 2017Review
- KIR3DL01 upregulation on gut natural killer cells in response to SIV infection of KIR- and MHC class I-defined rhesus macaques.PLoS pathogens · 2017Article
- HIV-1 adaptation to NK cell-mediated immune pressure.PLoS pathogens · 2017Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 4 countries.
Funding
Abstract
objectiveThe aim of this study was to assess the consequence of sequence variations in HLA-C03:04-presented HIV-1 p24 Gag epitopes on binding of the inhibitory natural killer (NK) cell receptor KIR2DL2 to HLA-C03:04.
designHIV-1 may possibly evade recognition by KIR+ NK cells through selection of sequence variants that interfere with the interactions of inhibitory killer cell immunoglobulin-like receptors (KIRs) and their target ligands on HIV-1 infected cells. KIR2DL2 is an inhibitory NK cell receptor that binds to a family of HLA-C ligands. Here, we investigated whether HIV-1 encodes for HLA-C03:04-restricted epitopes that alter KIR2DL2 binding.
methodsTapasin-deficient 721.220 cells expressing HLA-C03:04 were pulsed with overlapping peptides (10mers overlapped by nine amino acids, spanning the entire HIV-1 p24 Gag sequence) to identify peptides that stabilized HLA-C expression. The impact that sequence variation in HLA-C03:04-binding HIV-1 epitopes has on KIR2DL2 binding and KIR2DL2+ NK cell function was determined using KIR2DL2-Fc constructs and NK cell degranulation assays.
resultsSeveral novel HLA-C03:04 binding epitopes were identified within the HIV-1 p24 Gag consensus sequence. Three of these consensus sequence peptides (Gag144-152, Gag163-171 and Gag295-304) enabled binding of KIR2DL2 to HLA-C03:04 and resulted in inhibition of KIR2DL2+ primary NK cells. Furthermore, naturally occurring minor variants of epitope Gag295-304 enhanced KIR2DL2 binding to HLA-C03:04.
conclusionOur data show that naturally occurring sequence variations within HLA-C03:04-restricted HIV-1 p24 Gag epitopes can have a significant impact on the binding of inhibitory KIR receptors and primary NK cell function.
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