title: A catalytically inactive mutant of the deubiquitylase YOD-1 enhances antigen cross-presentation.
abstract: Antigen presenting cells (APCs) that express a catalytically inactive version of the deubiquitylase YOD1 (YOD1-C160S) present exogenous antigens more efficiently to CD8(+) T cells, both in vitro and in vivo. Compared with controls, immunization of YOD1-C160S mice led to greater expansion of specific CD8(+) T cells and showed improved control of infection with a recombinant -herpes virus, MHV-68, engineered to express SIINFEKL peptide, the ligand for the ovalbumin-specific TCR transgenic OT-I cells. Enhanced expansion of specific CD8(+) T cells was likewise observed on infection of YOD1-C160S mice with a recombinant influenza A virus expressing SIINFEKL. YOD1-C160S APCs retained antigen longer than did control APCs. Enhanced crosspresentation by YOD1-C160S APCs was transporter associated with antigen processing (TAP1)-independent but sensitive to inclusion of inhibitors of acidification and of the proteasome. The activity of deubiquitylating enzymes may thus help control antigenspecific CD8(+) T-cell responses during immunization.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
authors.forename: Sharvan
authors.initials: S
authors.lastname: Sehrawat
authors.forename: Paul-Albert
authors.initials: PA
authors.lastname: Koenig
authors.forename: Oktay
authors.initials: O
authors.lastname: Kirak
authors.forename: Christian
authors.initials: C
authors.lastname: Schlieker
authors.forename: Manuel
authors.initials: M
authors.lastname: Fankhauser
authors.forename: Hidde L
authors.initials: HL
authors.lastname: Ploegh
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D019264:Adoptive Transfer; D000818:Animals; D000938:Antigen-Presenting Cells / Q000201:enzymology / Q000276:immunology; D020126:Brefeldin A / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045142:Cross-Priming / Q000187:drug effects / Q000235:genetics; D005260:Female; D006863:Hydrogen-Ion Concentration; D007114:Immunization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020125:Mutation, Missense; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D018144:Rhadinovirus / Q000276:immunology / Q000472:pathogenicity; D043222:Ubiquitin Thiolesterase / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; C110366:OVA-8; D010446:Peptide Fragments; C486171:Tap1 protein, mouse; D020126:Brefeldin A; D010047:Ovalbumin; D043222:Ubiquitin Thiolesterase