Abstract
Epidemiological studies have shown the protective effect of KIR3DL1/HLA-Bw4 genotypes in human immunodeficiency virus type 1 (HIV-1) infection; however, the functional correlates for the protective effect remain unknown. We investigated whether human leukocyte antigen (HLA)-Bw4-presented HIV-1 peptides could affect the interaction between the inhibitory natural killer (NK) cell receptor KIR3DL1 and its ligand HLA-Bw4. Distinct HIV-1 epitopes differentially modulated the binding of KIR3DL1 to HLA-Bw4. Furthermore, cytotoxic T lymphocyte (CTL) escape mutations within the immunodominant HLA-B57 (Bw4)-restricted Gag epitope TSTLQEQIGW abrogated KIR3DL1 binding to HLA-B57, suggesting that sensing of CTL escape variants by NK cells can contribute to the protective effect of the KIR3DL1/HLA-Bw4 compound genotype.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Epitopes, T-Lymphocyte / chemistry
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Epitopes, T-Lymphocyte / genetics
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Epitopes, T-Lymphocyte / immunology*
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Gene Products, gag / chemistry
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Gene Products, gag / genetics*
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Gene Products, gag / immunology
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Gene Products, gag / metabolism
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Genetic Variation*
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HIV Infections / immunology
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HIV Infections / virology
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HIV-1 / genetics
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HIV-1 / immunology*
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HLA-B Antigens / genetics
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HLA-B Antigens / metabolism*
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Humans
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Immune Evasion
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Immunodominant Epitopes
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Jurkat Cells
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Killer Cells, Natural / immunology
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Killer Cells, Natural / metabolism
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Peptides / chemistry
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Peptides / genetics*
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Peptides / immunology
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Peptides / metabolism
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Point Mutation
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Protein Binding / drug effects
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Receptors, KIR3DL1 / metabolism*
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T-Lymphocytes, Cytotoxic / immunology
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T-Lymphocytes, Cytotoxic / metabolism
Substances
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Epitopes, T-Lymphocyte
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Gene Products, gag
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HLA-B Antigens
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HLA-Bw4 antigen
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Immunodominant Epitopes
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KIR3DL1 protein, human
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Peptides
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Receptors, KIR3DL1