Epitope-specific regulation of memory programming by differential duration of antigen presentation to influenza-specific CD8(+) T cells

Immunity. 2014 Jul 17;41(1):127-40. doi: 10.1016/j.immuni.2014.06.007.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigen Presentation / immunology*
  • Antigens, CD / immunology
  • CD11b Antigen / immunology
  • CD27 Ligand / biosynthesis
  • CD40 Antigens / antagonists & inhibitors
  • CD40 Antigens / genetics
  • CD40 Antigens / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • DNA-Directed RNA Polymerases / immunology
  • Dendritic Cells / immunology
  • Epitopes, T-Lymphocyte / immunology*
  • Histocompatibility Antigens Class I / pharmacology
  • Immunologic Memory / immunology*
  • Influenza A virus / immunology*
  • Integrin alpha Chains / immunology
  • Interferon-gamma / biosynthesis
  • Interleukin-2 / immunology
  • Interleukin-2 Receptor alpha Subunit / biosynthesis
  • Interleukin-2 Receptor alpha Subunit / genetics
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Minor Histocompatibility Antigens
  • Nucleoproteins / immunology
  • Orthomyxoviridae Infections / immunology
  • Signal Transduction / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology
  • Viral Core Proteins / immunology

Substances

  • Antigens, CD
  • CD11b Antigen
  • CD27 Ligand
  • CD40 Antigens
  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class I
  • Il2ra protein, mouse
  • Integrin alpha Chains
  • Interleukin-2
  • Interleukin-2 Receptor alpha Subunit
  • Minor Histocompatibility Antigens
  • Mr1 protein, mouse
  • Nucleoproteins
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Viral Core Proteins
  • alpha E integrins
  • Interferon-gamma
  • DNA-Directed RNA Polymerases