Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover
The key attributes of CD8+ T cell protective immunity in human immunodeficiency virus (HIV) infection remain unclear. We report that CD8+ T cell responses specific for Gag and, in particular, the immunodominant p24 epitope KK10 correlate with control of HIV-1 replication in human histocompatibility...
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| Published in | The Journal of experimental medicine Vol. 204; no. 10; pp. 2473 - 2485 |
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| Main Authors | , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Rockefeller University Press
01.10.2007
The Rockefeller University Press |
| Subjects | |
| Online Access | Get full text |
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| Abstract | The key attributes of CD8+ T cell protective immunity in human immunodeficiency virus (HIV) infection remain unclear. We report that CD8+ T cell responses specific for Gag and, in particular, the immunodominant p24 epitope KK10 correlate with control of HIV-1 replication in human histocompatibility leukocyte antigen (HLA)–B27 patients. To understand further the nature of CD8+ T cell–mediated antiviral efficacy, we performed a comprehensive study of CD8+ T cells specific for the HLA-B27–restricted epitope KK10 in chronic HIV-1 infection based on the use of multiparametric flow cytometry together with molecular clonotypic analysis and viral sequencing. We show that B27-KK10–specific CD8+ T cells are characterized by polyfunctional capabilities, increased clonal turnover, and superior functional avidity. Such attributes are interlinked and constitute the basis for effective control of HIV-1 replication. These data on the features of effective CD8+ T cells in HIV infection may aid in the development of successful T cell vaccines. |
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| AbstractList | The key attributes of CD8+ T cell protective immunity in human immunodeficiency virus (HIV) infection remain unclear. We report that CD8+ T cell responses specific for Gag and, in particular, the immunodominant p24 epitope KK10 correlate with control of HIV-1 replication in human histocompatibility leukocyte antigen (HLA)–B27 patients. To understand further the nature of CD8+ T cell–mediated antiviral efficacy, we performed a comprehensive study of CD8+ T cells specific for the HLA-B27–restricted epitope KK10 in chronic HIV-1 infection based on the use of multiparametric flow cytometry together with molecular clonotypic analysis and viral sequencing. We show that B27-KK10–specific CD8+ T cells are characterized by polyfunctional capabilities, increased clonal turnover, and superior functional avidity. Such attributes are interlinked and constitute the basis for effective control of HIV-1 replication. These data on the features of effective CD8+ T cells in HIV infection may aid in the development of successful T cell vaccines. The key attributes of CD8+ T cell protective immunity in human immunodeficiency virus (HIV) infection remain unclear. We report that CD8+ T cell responses specific for Gag and, in particular, the immunodominant p24 epitope KK10 correlate with control of HIV-1 replication in human histocompatibility leukocyte antigen (HLA)-B27 patients. To understand further the nature of CD8+ T cell-mediated antiviral efficacy, we performed a comprehensive study of CD8+ T cells specific for the HLA-B27-restricted epitope KK10 in chronic HIV-1 infection based on the use of multiparametric flow cytometry together with molecular clonotypic analysis and viral sequencing. We show that B27-KK10-specific CD8+ T cells are characterized by polyfunctional capabilities, increased clonal turnover, and superior functional avidity. Such attributes are interlinked and constitute the basis for effective control of HIV-1 replication. These data on the features of effective CD8+ T cells in HIV infection may aid in the development of successful T cell vaccines.The key attributes of CD8+ T cell protective immunity in human immunodeficiency virus (HIV) infection remain unclear. We report that CD8+ T cell responses specific for Gag and, in particular, the immunodominant p24 epitope KK10 correlate with control of HIV-1 replication in human histocompatibility leukocyte antigen (HLA)-B27 patients. To understand further the nature of CD8+ T cell-mediated antiviral efficacy, we performed a comprehensive study of CD8+ T cells specific for the HLA-B27-restricted epitope KK10 in chronic HIV-1 infection based on the use of multiparametric flow cytometry together with molecular clonotypic analysis and viral sequencing. We show that B27-KK10-specific CD8+ T cells are characterized by polyfunctional capabilities, increased clonal turnover, and superior functional avidity. Such attributes are interlinked and constitute the basis for effective control of HIV-1 replication. These data on the features of effective CD8+ T cells in HIV infection may aid in the development of successful T cell vaccines. The key attributes of CD8 + T cell protective immunity in human immunodeficiency virus (HIV) infection remain unclear. We report that CD8 + T cell responses specific for Gag and, in particular, the immunodominant p24 epitope KK10 correlate with control of HIV-1 replication in human histocompatibility leukocyte antigen (HLA)–B27 patients. To understand further the nature of CD8 + T cell–mediated antiviral efficacy, we performed a comprehensive study of CD8 + T cells specific for the HLA-B27–restricted epitope KK10 in chronic HIV-1 infection based on the use of multiparametric flow cytometry together with molecular clonotypic analysis and viral sequencing. We show that B27-KK10–specific CD8 + T cells are characterized by polyfunctional capabilities, increased clonal turnover, and superior functional avidity. Such attributes are interlinked and constitute the basis for effective control of HIV-1 replication. These data on the features of effective CD8 + T cells in HIV infection may aid in the development of successful T cell vaccines. |
| Author | Papagno, Laura Marcelin, Anne-Geneviève Schnuriger, Aurélie Bornstein, Ethan Rouzioux, Christine Sauce, Delphine Agut, Henri Almeida, Jorge R. Costagliola, Dominique Autran, Brigitte Arkoub, Zaïna Aït Asher, Tedi E. Price, David A. Appay, Victor Samri, Assia Theodorou, Ioannis Douek, Daniel |
| AuthorAffiliation | 1 Cellular Immunology Laboratory, U543, Institut National de la Santé et de la Recherche Médicale (INSERM), Avenir Group, 2 Virology Laboratory, UPRES EA2387, and 3 U720, INSERM, Hôpital Pitié-Salpêtrière, Université Pierre et Marie Curie-Paris6, 75013 Paris, France 6 Virology Laboratory, Hôpital Necker-Enfants Malades, Université René Descartes-Paris5, 75015 Paris, France 4 Human Immunology Section, Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892 5 Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, England, UK |
| AuthorAffiliation_xml | – name: 6 Virology Laboratory, Hôpital Necker-Enfants Malades, Université René Descartes-Paris5, 75015 Paris, France – name: 4 Human Immunology Section, Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892 – name: 5 Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, England, UK – name: 1 Cellular Immunology Laboratory, U543, Institut National de la Santé et de la Recherche Médicale (INSERM), Avenir Group, 2 Virology Laboratory, UPRES EA2387, and 3 U720, INSERM, Hôpital Pitié-Salpêtrière, Université Pierre et Marie Curie-Paris6, 75013 Paris, France |
| Author_xml | – sequence: 1 givenname: Jorge R. surname: Almeida fullname: Almeida, Jorge R. – sequence: 2 givenname: David A. surname: Price fullname: Price, David A. – sequence: 3 givenname: Laura surname: Papagno fullname: Papagno, Laura – sequence: 4 givenname: Zaïna Aït surname: Arkoub fullname: Arkoub, Zaïna Aït – sequence: 5 givenname: Delphine surname: Sauce fullname: Sauce, Delphine – sequence: 6 givenname: Ethan surname: Bornstein fullname: Bornstein, Ethan – sequence: 7 givenname: Tedi E. surname: Asher fullname: Asher, Tedi E. – sequence: 8 givenname: Assia surname: Samri fullname: Samri, Assia – sequence: 9 givenname: Aurélie surname: Schnuriger fullname: Schnuriger, Aurélie – sequence: 10 givenname: Ioannis surname: Theodorou fullname: Theodorou, Ioannis – sequence: 11 givenname: Dominique surname: Costagliola fullname: Costagliola, Dominique – sequence: 12 givenname: Christine surname: Rouzioux fullname: Rouzioux, Christine – sequence: 13 givenname: Henri surname: Agut fullname: Agut, Henri – sequence: 14 givenname: Anne-Geneviève surname: Marcelin fullname: Marcelin, Anne-Geneviève – sequence: 15 givenname: Daniel surname: Douek fullname: Douek, Daniel – sequence: 16 givenname: Brigitte surname: Autran fullname: Autran, Brigitte – sequence: 17 givenname: Victor surname: Appay fullname: Appay, Victor |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/17893201$$D View this record in MEDLINE/PubMed https://hal.science/hal-02455369$$DView record in HAL |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 PMCID: PMC2118466 CORRESPONDENCE Victor Appay: appay@chups.jussieu.fr Abbreviations used: APC, allophycocyanin; CCR, CC chemokine receptor; cVL, cell-associated HIV–DNA load; MFI, median fluorescence intensity; MIP, macrophage inflammatory protein; PD-1, programmed death–1; pVL, plasma HIV–RNA load; SFU, spot-forming unit. |
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| Snippet | The key attributes of CD8+ T cell protective immunity in human immunodeficiency virus (HIV) infection remain unclear. We report that CD8+ T cell responses... The key attributes of CD8 + T cell protective immunity in human immunodeficiency virus (HIV) infection remain unclear. We report that CD8 + T cell responses... |
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| SubjectTerms | Amino Acid Sequence CD57 Antigens - metabolism CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - pathology Cell Proliferation Cellular Senescence Gene Products, gag - immunology HIV Infections - immunology HIV Infections - metabolism HIV Infections - pathology HIV-1 - physiology HLA-B27 Antigen - chemistry HLA-B27 Antigen - immunology Humans Immunology Life Sciences Lymphocyte Count Molecular Sequence Data Virus Replication |
| Title | Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover |
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