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

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


  • Sehrawat S
  • Koenig PA
  • Kirak O
  • Schlieker C
  • Fankhauser M
  • Ploegh HL



Publication Data

February 14, 2013

Associated Grants


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