title: Differential use of autophagy by primary dendritic cells specialized in cross-presentation.
abstract: Antigen-presenting cells survey their environment and present captured antigens bound to major histocompatibility complex (MHC) molecules. Formation of MHC-antigen complexes occurs in specialized compartments where multiple protein trafficking routes, still incompletely understood, converge. Autophagy is a route that enables the presentation of cytosolic antigen by MHC class II molecules. Some reports also implicate autophagy in the presentation of extracellular, endocytosed antigen by MHC class I molecules, a pathway termed "cross-presentation." The role of autophagy in cross-presentation is controversial. This may be due to studies using different types of antigen presenting cells for which the use of autophagy is not well defined. Here we report that active use of autophagy is evident only in DC subtypes specialized in cross-presentation. However, the contribution of autophagy to cross-presentation varied depending on the form of antigen: it was negligible in the case of cell-associated antigen or antigen delivered via receptor-mediated endocytosis, but more prominent when the antigen was a soluble protein. These findings highlight the differential use of autophagy and its machinery by primary cells equipped with specific immune function, and prompt careful reassessment of the participation of this endocytic pathway in antigen cross-presentation.
authors.affiliation: a Walter and Eliza Hall Institute ; Parkville , VIC Australia.
authors.forename: Justine D
authors.initials: JD
authors.lastname: Mintern
authors.forename: Christophe
authors.initials: C
authors.lastname: Macri
authors.forename: Wei Jin
authors.initials: WJ
authors.lastname: Chin
authors.forename: Scott E
authors.initials: SE
authors.lastname: Panozza
authors.forename: Elodie
authors.initials: E
authors.lastname: Segura
authors.forename: Natalie L
authors.initials: NL
authors.lastname: Patterson
authors.forename: Peter
authors.initials: P
authors.lastname: Zeller
authors.forename: Dorothee
authors.initials: D
authors.lastname: Bourges
authors.forename: Sammy
authors.initials: S
authors.lastname: Bedoui
authors.forename: Paul J
authors.initials: PJ
authors.lastname: McMillan
authors.forename: Adi
authors.initials: A
authors.lastname: Idris
authors.forename: Cameron J
authors.initials: CJ
authors.lastname: Nowell
authors.forename: Andrew
authors.initials: A
authors.lastname: Brown
authors.forename: Kristen J
authors.initials: KJ
authors.lastname: Radford
authors.forename: Angus Pr
authors.initials: AP
authors.lastname: Johnston
authors.forename: Jose A
authors.initials: JA
authors.lastname: Villadangos
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001343:Autophagy / Q000276:immunology*; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D004705:Endocytosis / Q000276:immunology / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006801:Humans; D051379:Mice
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II
keywords: 3-MA, 3-methyladenine; Atg7-DC CKO, Atg7 DC conditional knockout; BafA, bafilomycin A1; CD, cluster of differentiation; CTL, cytotoxic T lymphocyte; DALIS, dendritic cell aggresome-like inducible structures; DC, dendritic cell; IFC imaging flow cytometry; LAP, LC3 associated phagocytosis; LC3B, microtubule-associated protein 1 light chain 3 β; MHC I, major histocompatibility complex class I; MHC II, major histocompatibility complex class II; OT-I, OVA-specific CD8+ T cell; OT-II, OVA-specific CD4+ T cell; SIM, structured illumination microscopy.; OVA, ovalbumin; antigen presentation; autophagy; dendritic cells; green fluorescent protein, GFP