Prolonged antigen presentation by immune complex-binding dendritic cells programs the proliferative capacity of memory CD8 T cells

J Exp Med. 2014 Jul 28;211(8):1637-55. doi: 10.1084/jem.20131692. Epub 2014 Jul 7.

Abstract

The commitment of naive CD8 T cells to effector or memory cell fates can occur after a single day of antigenic stimulation even though virus-derived antigens (Ags) are still presented by DCs long after acute infection is resolved. However, the effects of extended Ag presentation on CD8 T cells are undefined and the mechanisms that regulate prolonged Ag presentation are unknown. We showed that the sustained presentation of two different epitopes from influenza virus by DCs prevented the premature contraction of the primary virus-specific CD8 T cell response. Although prolonged Ag presentation did not alter the number of memory CD8 T cells that developed, it was essential for programming the capacity of these cells to proliferate, produce cytokines, and protect the host after secondary challenge. Importantly, prolonged Ag presentation by DCs was dependent on virus-specific, isotype-switched antibodies (Abs) that facilitated the capture and cross-presentation of viral Ags by FcγR-expressing DCs. Collectively, our results demonstrate that B cells and Abs can regulate the quality and functionality of a subset of antiviral CD8 T cell memory responses and do so by promoting sustained Ag presentation by DCs during the contraction phase of the primary T cell response.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Viral / immunology
  • Antibody Specificity / immunology
  • Antigen Presentation / immunology*
  • Antigen-Antibody Complex / immunology*
  • Antigens, Viral / immunology
  • B-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Cytidine Deaminase / deficiency
  • Cytidine Deaminase / metabolism
  • Dendritic Cells / immunology*
  • Humans
  • Immunologic Memory / immunology
  • Influenza, Human / immunology
  • Influenza, Human / virology
  • Lymph Nodes / cytology
  • Lymphocyte Depletion
  • Mice
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / virology
  • Receptors, IgG / metabolism

Substances

  • Antibodies, Viral
  • Antigen-Antibody Complex
  • Antigens, Viral
  • Fcgr1 protein, mouse
  • Receptors, IgG
  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase