Abstract
We eventually isolated two different clonotypic CD8 T cell subsets recognizing an HIV Pol-derived epitope peptide (IPLTEEAEL) in association with HLA-B35 from a chronic HIV-infected patient. By kinetic analysis experiments, the subsets showed a >3-fold difference in half-lives for the HLA tetramer in complex with the Pol peptide. In functional assays in vitro and ex vivo, both subsets showed substantial functional avidity toward peptide-loaded cells. However, the high affinity subset did not show cytolytic activity, cytokine production, or proliferation activity toward HIV-infected cells, whereas the moderate affinity one showed potent activities. Furthermore, using ectopic expression of each of the TCR genes into primary human CD8 T cells, the CD8 T cells transduced with the high affinity TCR showed greater binding activity toward the tetramer and impaired cytotoxic activity toward HIV-infected cells, corroborating the results obtained with parental CD8 T cells. Taken together, these data indicate that impaired responsiveness of T cells toward HIV-infected cells can occur at the level of TCR-ligand interactions, providing us further insight into the immune evasion mechanisms by HIV.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / virology*
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Clone Cells
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Coculture Techniques
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Cytotoxicity, Immunologic* / genetics
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Epitopes, T-Lymphocyte / biosynthesis
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Epitopes, T-Lymphocyte / immunology*
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Epitopes, T-Lymphocyte / metabolism
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Gene Products, pol / biosynthesis
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Gene Products, pol / immunology
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Gene Products, pol / metabolism
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Genes, T-Cell Receptor alpha
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Genes, T-Cell Receptor beta
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HIV / immunology*
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Humans
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Kinetics
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Ligands
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Lymphocyte Activation / genetics
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Molecular Sequence Data
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Protein Binding / genetics
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Protein Binding / immunology
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Receptors, Antigen, T-Cell, alpha-beta / metabolism*
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Receptors, Antigen, T-Cell, alpha-beta / physiology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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T-Lymphocyte Subsets / virology*
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T-Lymphocytes, Cytotoxic / immunology
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T-Lymphocytes, Cytotoxic / metabolism
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T-Lymphocytes, Cytotoxic / virology
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Transduction, Genetic
Substances
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Epitopes, T-Lymphocyte
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Gene Products, pol
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Ligands
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Receptors, Antigen, T-Cell, alpha-beta
Associated data
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GENBANK/AB164056
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GENBANK/AB164057
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GENBANK/AB164620
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GENBANK/AB164621