Dendritic Cell Presentation of Antigens From Apoptotic Cells in a Proinflammatory Context: Role of Opsonizing anti-beta2-glycoprotein I Antibodies

Arthritis Rheum. 1999 Jul;42(7):1412-20. doi: 10.1002/1529-0131(199907)42:7<1412::AID-ANR15>3.0.CO;2-T.

Abstract

Objective: To verify whether opsonization of apoptotic cells skews the outcome of apoptotic cell antigen presentation by dendritic cells (DCs).

Methods: RMA cells, which were engineered with a mutant ovalbumin (OVA) protein and were devoid of the leader secretory sequence (OVA-RMA), underwent ultraviolet irradiation to induce apoptosis. Binding of anti-beta2-glycoprotein I antibodies (anti-beta2GPI) and phagocytosis of apoptotic cells were assessed by flow cytometry and confocal microscopy. Presentation of processing antigens and major histocompatibility complex (MHC) class II-restricted or MHC class I-restricted antigens was assessed using OVA-specific T cell hybridomas.

Results: Anti-beta2GPI facilitated presentation of epitopes from internalized apoptotic cells to MHC class II-restricted, but not to class I-restricted, T lymphocytes. DCs challenged with supernatants of apoptotic cells did not activate OVA-specific T cells, making it unlikely that anti-beta2GPI complexed with antigen released from dying cells plays a role in antigen presentation. DCs challenged with low numbers of anti-beta2GPI-opsonized apoptotic cells secreted interleukin-1beta (IL-1beta), tumor necrosis factor alpha, and IL-10 in an autocrine/paracrine manner.

Conclusion: Opsonization influences the outcome of the disposal of low numbers of apoptotic cells by DCs. This implies that soluble factors bound to apoptotic cells modulate their immunogenicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / physiology
  • Antibodies, Antiphospholipid / blood
  • Antigen Presentation
  • Apoptosis / immunology*
  • Autoimmunity / physiology
  • Cell Line
  • Dendritic Cells / immunology*
  • Glycoproteins / immunology*
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Interleukin-1 / metabolism
  • Interleukin-10 / metabolism
  • Microscopy, Confocal
  • Opsonin Proteins / metabolism*
  • T-Lymphocytes / immunology
  • Tumor Cells, Cultured
  • beta 2-Glycoprotein I

Substances

  • Antibodies
  • Antibodies, Antiphospholipid
  • Glycoproteins
  • Histocompatibility Antigens Class II
  • Interleukin-1
  • Opsonin Proteins
  • beta 2-Glycoprotein I
  • Interleukin-10