title: Targeting antigen to bone marrow stromal cell-2 expressed by conventional and plasmacytoid dendritic cells elicits efficient antigen presentation.
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.
authors.affiliation: Walter and Eliza Hall Institute, Parkville, Victoria, Australia.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Moffat
authors.forename: Elodie
authors.initials: E
authors.lastname: Segura
authors.forename: Gabriela
authors.initials: G
authors.lastname: Khoury
authors.forename: Irene
authors.initials: I
authors.lastname: Caminschi
authors.forename: Paul U
authors.initials: PU
authors.lastname: Cameron
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Lewin
authors.forename: Jose A
authors.initials: JA
authors.lastname: Villadangos
authors.forename: Justine D
authors.initials: JD
authors.lastname: Mintern
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D058851:GPI-Linked Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D011956:Receptors, Cell Surface / Q000378:metabolism; D014158:Transcription, Genetic; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D000941:Antigens; D015703:Antigens, CD; D000954:Antigens, Surface; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C513868:BST2 protein, mouse