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

Blood. 2013 Feb 14;121(7):1145-56. doi: 10.1182/blood-2012-08-447409. Epub 2012 Dec 13.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP-Binding Cassette Transporters / deficiency
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / immunology
  • Adoptive Transfer
  • Animals
  • Antigen-Presenting Cells / enzymology
  • Antigen-Presenting Cells / immunology
  • Brefeldin A / pharmacology
  • CD8-Positive T-Lymphocytes / immunology
  • Cross-Priming* / drug effects
  • Cross-Priming* / genetics
  • Female
  • Hydrogen-Ion Concentration
  • Immunization
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Mutation, Missense*
  • Ovalbumin / immunology
  • Peptide Fragments / immunology
  • Rhadinovirus / immunology
  • Rhadinovirus / pathogenicity
  • Ubiquitin Thiolesterase / genetics*
  • Ubiquitin Thiolesterase / immunology*
  • Ubiquitin Thiolesterase / metabolism

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP-Binding Cassette Transporters
  • OVA-8
  • Peptide Fragments
  • Tap1 protein, mouse
  • Brefeldin A
  • Ovalbumin
  • Ubiquitin Thiolesterase