title: Recruitment of Rab27a to phagosomes controls microbial antigen cross-presentation by dendritic cells.
abstract: Polyreactive immunoglobulins (Ig) and complement components are present in tissues and blood of healthy individuals. They facilitate pathogen uptake and inactivation in lysosomes of phagocytes and thereby provide rapid protection against infection. Dendritic cells (DCs) are phagocytes that can acquire peptides from phagocytosed antigen to elicit cytotoxic immune responses by CD8(+) T lymphocytes. The mechanisms that select peptides for cross-presentation are not fully resolved. Here we investigated the role of polyreactive Ig and complement in directing phagosomal antigen processing for cross-presentation. Phagocytosis facilitated by serum opsonization required the presence of Ig for effective antigen cross-presentation of microbe-derived antigen. The presence of complement C3 in serum promoted phagocytosis, yet phagosomes were defective in antigen degradation. The small GTPase Rab27a was recently implicated in antigen cross-presentation and was rapidly recruited to phagosomes only when Ig was present. Our data suggest that prebinding of antigen by polyreactive Ig potentiates the efficiency of antigen cross-presentation to CD8(+) T cells through recruitment of Rab27a.
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
authors.forename: Seong Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Annelies
authors.initials: A
authors.lastname: Visser
authors.forename: Carin
authors.initials: C
authors.lastname: Cruijsen
authors.forename: Adrianus W M
authors.initials: AW
authors.lastname: van der Velden
authors.forename: Marianne
authors.initials: M
authors.lastname: Boes
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003176:Complement C3 / Q000276:immunology; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology; D005434:Flow Cytometry; D007136:Immunoglobulins / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018613:Microscopy, Confocal; D010587:Phagocytosis / Q000276:immunology; D010588:Phagosomes / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D000075745:rab27 GTP-Binding Proteins
chemical_list: D000942:Antigens, Bacterial; D003176:Complement C3; D007136:Immunoglobulins; D000075745:rab27 GTP-Binding Proteins; C512962:Rab27a protein, mouse; D020691:rab GTP-Binding Proteins
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