Prolonged antigen survival and cytosolic export in cross-presenting human gammadelta T cells.
Human blood Vgamma9Vdelta2 T cells respond to signals from microbes and tumors and subsequently differentiate into professional antigen-presenting cells (gammadelta T-APCs) for induction of CD4(+) and CD8(+) T cell responses. gammadelta T-APCs readily take up and degrade exogenous soluble protein for peptide loading on MHC I, in a process termed antigen cross-presentation. The mechanisms underlying antigen cross-presentation are ill-defined, most notably in human dendritic cells (DCs), and no study has addressed this process in gammadelta T-APCs. Here we show that intracellular protein degradation and endosomal acidification were significantly delayed in gammadelta T-APCs compared with human monocyte-derived DCs (moDCs). Such conditions are known to favor antigen cross-presentation. In both gammadelta T-APCs and moDCs, internalized antigen was transported across insulin-regulated aminopeptidase (IRAP)-positive early and late endosomes; however, and in contrast to various human DC subsets, gammadelta T-APCs efficiently translocated soluble antigen into the cytosol for processing via the cytosolic proteasome-dependent cross-presentation pathway. Of note, gammadelta T-APCs cross-presented influenza antigen derived from virus-infected cells and from free virus particles. The robust cross-presentation capability appears to be a hallmark of gammadelta T-APCs and underscores their potential application in cellular immunotherapy.
Meuter
Simone
S
Department of Infection, Immunity and Biochemistry, School of Medicine, Cardiff University, Cardiff, UK. moserb@cardiff.ac.uk
Eberl
Matthias
M
Moser
Bernhard
B
D000143:Acids / Q000378:metabolism; D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology / Q000821:virology; D000941:Antigens / Q000276:immunology*; D002417:Cattle; D045142:Cross-Priming / Q000276:immunology*; D003600:Cytosol / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D009980:Influenza A virus / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D021381:Protein Transport / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D012710:Serum Albumin, Bovine / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014771:Virion / Q000276:immunology; D038301:Virus Inactivation
D000143:Acids; D000941:Antigens; D016692:Receptors, Antigen, T-Cell, gamma-delta; D012710:Serum Albumin, Bovine; D046988:Proteasome Endopeptidase Complex