Circulating specific antibodies enhance systemic cross-priming by delivery of complexed antigen to dendritic cells in vivo

Eur J Immunol. 2012 Mar;42(3):598-606. doi: 10.1002/eji.201141613.

Abstract

Increasing evidence suggests that antibodies can have stimulatory effects on T-cell immunity. However, the contribution of circulating antigen-specific antibodies on MHC class I cross-priming in vivo has not been conclusively established. Here, we defined the role of circulating antibodies in cross-presentation of antigen to CD8(+) T cells. Mice with hapten-specific circulating antibodies, but naϊve for the T-cell antigen, were infused with haptenated antigen and CD8(+) T-cell induction was measured. Mice with circulating hapten-specific antibodies showed significantly enhanced cross-presentation of the injected antigen compared with mice that lacked these antibodies. The enhanced cross-presentation in mice with circulating antigen-specific antibodies was associated with improved antigen capture by APCs. Importantly, CD11c(+) APCs were responsible for the enhanced and sustained cross-presentation, although CD11c(-) APCs had initially captured a significant amount of the injected antigen. Thus, in vivo formation of antigen-antibody immune complexes improves MHC class I cross-presentation, and CD8(+) T-cell activation, demonstrating that humoral immunity can aid the initiation of systemic cellular immunity. These findings have important implications for the understanding of the action of therapeutic antibodies against tumor-associated antigens intensively used in the clinic nowadays.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Antibody Complex / immunology*
  • Antigens, Neoplasm / immunology
  • CD11c Antigen / immunology*
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cross-Priming / immunology
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Flow Cytometry
  • Haptens / immunology
  • Histocompatibility Antigens Class I / immunology
  • Immunity, Cellular / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Ovalbumin / immunology
  • Serum Albumin, Bovine / immunology

Substances

  • Antigen-Antibody Complex
  • Antigens, Neoplasm
  • CD11c Antigen
  • Haptens
  • Histocompatibility Antigens Class I
  • Serum Albumin, Bovine
  • Ovalbumin