title: Epitope-specific regulation of memory programming by differential duration of antigen presentation to influenza-specific CD8(+) T cells.
abstract: Memory CD8(+) T cells are programmed during the primary response for robust secondary responsiveness. Here we show that CD8(+) T cells responding to different epitopes of influenza virus received qualitatively different signals during the primary response that altered their secondary responsiveness. Nucleoprotein (NP)-specific CD8(+) T cells encountered antigen on CD40-licensed, CD70-expressing, CD103(-)CD11b(hi) dendritic cells (DCs) at later times in the primary response. As a consequence, they maintained CD25 expression and responded to interleukin-2 (IL-2) and CD27, which together programmed their robust secondary proliferative capacity and interferon-γ (IFN-γ)-producing ability. In contrast, polymerase (PA)-specific CD8(+) T cells did not encounter antigen-bearing, CD40-activated DCs at later times in the primary response, did not receive CD27 and CD25 signals, and were not programmed to become memory CD8(+) T cells with strong proliferative and cytokine-producing ability. As a result, CD8(+) T cells responding to abundant antigens, like NP, dominated the secondary response.
authors.affiliation: Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: André
authors.initials: A
authors.lastname: Ballesteros-Tato
authors.affiliation: Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Beatriz
authors.initials: B
authors.lastname: León
authors.affiliation: Vaccine Research Institute of San Diego, San Diego, CA 92109, USA.
authors.forename: Byung O
authors.initials: BO
authors.lastname: Lee
authors.affiliation: Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Frances E
authors.initials: FE
authors.lastname: Lund
authors.affiliation: Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Electronic address: randallt@uab.edu.
authors.forename: Troy D
authors.initials: TD
authors.lastname: Randall
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology; D039481:CD11b Antigen / Q000276:immunology; D053282:CD27 Ligand / Q000096:biosynthesis; D019013:CD40 Antigens / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D012321:DNA-Directed RNA Polymerases / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000494:pharmacology; D007156:Immunologic Memory / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology*; D039001:Integrin alpha Chains / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015778:Minor Histocompatibility Antigens; D009698:Nucleoproteins / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology; D014758:Viral Core Proteins / Q000276:immunology
chemical_list: D015703:Antigens, CD; D039481:CD11b Antigen; D053282:CD27 Ligand; D019013:CD40 Antigens; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; C508018:Il2ra protein, mouse; D039001:Integrin alpha Chains; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D015778:Minor Histocompatibility Antigens; C490628:Mr1 protein, mouse; D009698:Nucleoproteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014758:Viral Core Proteins; C091367:alpha E integrins; D007371:Interferon-gamma; D012321:DNA-Directed RNA Polymerases