title: Despite differences between dendritic cells and Langerhans cells in the mechanism of papillomavirus-like particle antigen uptake, both cells cross-prime T cells.
abstract: As human papillomavirus-like particles (HPV-VLP) represent a promising vaccine delivery vehicle, delineation of the interaction of VLP with professional APC should improve vaccine development. Differences in the capacity of VLP to signal dendritic cells (DC) and Langerhans cells (LC) have been demonstrated, and evidence has been presented for both clathrin-coated pits and proteoglycans (PG) in the uptake pathway of VLP into epithelial cells. Therefore, we compared HPV-VLP uptake mechanisms in human monocyte-derived DC and LC, and their ability to cross-present HPV VLP-associated antigen in the MHC class I pathway. DC and LC each took up virus-like particles (VLP). DC uptake of and signalling by VLP was inhibited by amiloride or cytochalasin D (CCD), but not by filipin treatment, and was blocked by several sulfated and non-sulfated polysaccharides and anti-CD16. In contrast, LC uptake was inhibited only by filipin, and VLP in LC were associated with caveolin, langerin, and CD1a. These data suggest fundamentally different routes of VLP uptake by DC and LC. Despite these differences, VLP taken up by DC and LC were each able to prime naive CD8(+) T cells and induce cytolytic effector T cells in vitro.
authors.affiliation: Centre for Immunology and Cancer Research, Princess Alexandra Hospital, University of Queensland, Brisbane, QLD 4102, Australia.
authors.forename: Mengyong
authors.initials: M
authors.lastname: Yan
authors.forename: Judy
authors.initials: J
authors.lastname: Peng
authors.forename: Ibtissam A
authors.initials: IA
authors.lastname: Jabbar
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Liu
authors.forename: Luis
authors.initials: L
authors.lastname: Filgueira
authors.forename: Ian H
authors.initials: IH
authors.lastname: Frazer
authors.forename: Ranjeny
authors.initials: R
authors.lastname: Thomas
mesh_terms: D000584:Amiloride; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000821:virology; D015703:Antigens, CD; D000954:Antigens, Surface / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D036022:Capsid Proteins; D045142:Cross-Priming; D015638:Cytochalasin D; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D006801:Humans; D007801:Langerhans Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000276:immunology / Q000378:metabolism; D019384:Nucleic Acid Synthesis Inhibitors; D009856:Oncogene Proteins, Viral / Q000276:immunology / Q000378:metabolism; D027383:Papillomaviridae / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology; D014779:Virus Replication / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; C121916:CD207 protein, human; D036022:Capsid Proteins; C114580:HPV L1 protein, Human papillomavirus; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D019384:Nucleic Acid Synthesis Inhibitors; D009856:Oncogene Proteins, Viral; D011956:Receptors, Cell Surface; D017452:Receptors, IgG; D015638:Cytochalasin D; D000584:Amiloride