title: Differential uptake and cross-presentation of soluble and necrotic cell antigen by human DC subsets.
abstract: Cross-presentation is the mechanism by which exogenous Ag is processed for recognition by CD8(+) T cells. Murine CD8α(+) DCs are specialized at cross-presenting soluble and cellular Ag, but in humans this process is poorly characterized. In this study, we examined uptake and cross-presentation of soluble and cellular Ag by human blood CD141(+) DCs, the human equivalent of mouse CD8α(+) DCs, and compared them with human monocyte-derived DCs (MoDCs) and blood CD1c(+) DC subsets. MoDCs were superior in their capacity to internalize and cross-present soluble protein whereas CD141(+) DCs were more efficient at ingesting and cross-presenting cellular Ag. Whilst cross-presentation by CD1c(+) DCs and CD141(+) DCs was dependent on the proteasome, and hence cytosolic translocation, cross-presentation by MoDCs was not. Inhibition of endosomal acidification enhanced cross-presentation by CD1c(+) DCs and MoDCs but not by CD141(+) DCs. These data demonstrate that CD1c(+) DCs, CD141(+) DCs, and MoDCs are capable of cross-presentation; however, they do so via different mechanisms. Moreover, they demonstrate that human CD141(+) DCs, like their murine CD8α(+) DC counterparts, are specialized at cross-presenting cellular Ag, most likely mediated by an enhanced capacity to ingest cellular Ag combined with subtle changes in lysosomal pH during Ag processing and use of the cytosolic pathway.
authors.affiliation: Mater Research Institute, University of Queensland, Brisbane, Queensland, Australia.|School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Meng-Chieh
authors.initials: MC
authors.lastname: Chiang
authors.affiliation: Mater Research Institute, University of Queensland, Brisbane, Queensland, Australia.|Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.|School of Medicine, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Kirsteen M
authors.initials: KM
authors.lastname: Tullett
authors.affiliation: Mater Research Institute, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Yoke Seng
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Mater Research Institute, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Adi
authors.initials: A
authors.lastname: Idris
authors.affiliation: Mater Research Institute, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Yitian
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Mater Research Institute, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Kylie J
authors.initials: KJ
authors.lastname: McDonald
authors.affiliation: Mater Research Institute, University of Queensland, Brisbane, Queensland, Australia.|School of Medicine, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Kassianos
authors.affiliation: Mater Research Institute, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Ingrid M
authors.initials: IM
authors.lastname: Leal Rojas
authors.affiliation: Mater Research Institute, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Varinder
authors.initials: V
authors.lastname: Jeet
authors.affiliation: School of Medicine, University of Queensland, Brisbane, Queensland, Australia.|Department of Immunology, Monash University, Melbourne, Victoria, Australia.
authors.forename: Mireille H
authors.initials: MH
authors.lastname: Lahoud
authors.affiliation: Mater Research Institute, University of Queensland, Brisbane, Queensland, Australia.|School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Kristen J
authors.initials: KJ
authors.lastname: Radford
mesh_terms: D018949:Antigens, CD1 / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D001775:Blood Circulation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D045142:Cross-Priming; D003713:Dendritic Cells / Q000276:immunology*; D004705:Endocytosis; D006801:Humans; D009000:Monocytes / Q000276:immunology; D009336:Necrosis; D010750:Phosphoproteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D021381:Protein Transport; D012995:Solubility; D018180:Thrombomodulin; D014763:Viral Matrix Proteins / Q000378:metabolism*
chemical_list: D018949:Antigens, CD1; D000954:Antigens, Surface; C419394:CD1b antigen; D010750:Phosphoproteins; C546931:THBD protein, human; D018180:Thrombomodulin; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; D046988:Proteasome Endopeptidase Complex
keywords: Antigen processing; Cross-presentation; Human dendritic cells