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A catalytically inactive mutant of the deubiquitylase YOD-1 enhances antigen cross-presentation.

Blood | Feb 14, 2013

http://www.ncbi.nlm.nih.gov/pubmed/23243279

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.

Pubmed ID: 23243279 RIS Download

Mesh terms: ATP-Binding Cassette Transporters | Adoptive Transfer | Animals | Antigen-Presenting Cells | Brefeldin A | CD8-Positive T-Lymphocytes | Cross-Priming | Female | Hydrogen-Ion Concentration | Immunization | Male | Mice | Mice, Inbred C57BL | Mice, Knockout | Mice, Transgenic | Mutation, Missense | Ovalbumin | Peptide Fragments | Rhadinovirus | Ubiquitin Thiolesterase

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Mouse Genome Informatics (Data, Gene Annotation)

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