Targeting antigen to bone marrow stromal cell-2 expressed by conventional and plasmacytoid dendritic cells elicits efficient antigen presentation

Eur J Immunol. 2013 Mar;43(3):595-605. doi: 10.1002/eji.201242799. Epub 2013 Feb 6.

Abstract

Bone marrow stromal cell-2 (BST-2) has major roles in viral tethering and modulation of interferon production. Here we investigate BST-2 as a receptor for the delivery of antigen to dendritic cells (DCs). We show that BST-2 is expressed by a panel of mouse and human DC subsets, particularly under inflammatory conditions. The outcome of delivering antigen to BST-2 expressed by steady state and activated plasmacytoid DC (pDC) or conventional CD8(+) and CD8(-) DCs was determined. T-cell responses were measured for both MHC class I (MHCI) and MHC class II (MHCII) antigen presentation pathways in vitro. Delivering antigen via BST-2 was compared with that via receptors DEC205 or Siglec-H. We show that despite a higher antigen load and faster receptor internalisation, when antigen is delivered to steady state or activated pDC via BST-2, BST-2-targeted activated conventional DCs present antigen more efficiently. Relative to DEC205, BST-2 was inferior in its capacity to deliver antigen to the MHCI cross-presentation pathway. In contrast, BST-2 was superior to Siglec-H at initiating either MHCI or MHCII antigen presentation. In summary, BST-2 is a useful receptor to target with antigen, given its broad expression pattern and ability to access both MHCI and MHCII presentation pathways with relative efficiency.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology*
  • Antigens / immunology
  • Antigens / metabolism
  • Antigens, CD / genetics*
  • Antigens, CD / immunology
  • Antigens, CD / metabolism*
  • Antigens, Surface / genetics
  • Antigens, Surface / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / immunology
  • GPI-Linked Proteins / metabolism
  • Gene Expression Profiling
  • Humans
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Receptors, Cell Surface / metabolism
  • Transcription, Genetic

Substances

  • Antigens
  • Antigens, CD
  • Antigens, Surface
  • BST2 protein, human
  • BST2 protein, mouse
  • GPI-Linked Proteins
  • Membrane Glycoproteins
  • Receptors, Cell Surface