Defective cross-presentation of viral antigens in GILT-free mice

Science. 2010 Jun 11;328(5984):1394-8. doi: 10.1126/science.1189176.


Gamma-interferon-inducible lysosomal thiolreductase (GILT) promotes major histocompatibility complex (MHC) class II-restricted presentation of exogenous antigens containing disulfide bonds. Here, we show that GILT also facilitates MHC class I-restricted recognition of such antigens by CD8+ T cells, or cross-presentation. GILT is essential for cross-presentation of a CD8+ T cell epitope of glycoprotein B (gB) from herpes simplex virus 1 (HSV-1) but not for its presentation by infected cells. Initiation of the gB-specific CD8+ T cell response during HSV-1 infection, or cross-priming, is highly GILT-dependent, as is initiation of the response to the envelope glycoproteins of influenza A virus. Efficient cross-presentation of disulfide-rich antigens requires a complex pathway involving GILT-mediated reduction, unfolding, and partial proteolysis, followed by translocation into the cytosol for proteasomal processing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Antigen Presentation
  • Antigens, Viral / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cross-Priming*
  • Cytosol / metabolism
  • Dendritic Cells / immunology
  • Epitopes, T-Lymphocyte / immunology
  • H-2 Antigens / immunology
  • HeLa Cells
  • Herpes Simplex / immunology*
  • Herpes Simplex / metabolism
  • Herpesvirus 1, Human / immunology*
  • Humans
  • Influenza A virus / immunology
  • Mice
  • Orthomyxoviridae Infections / immunology
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism*
  • Oxidoreductases Acting on Sulfur Group Donors
  • Proteasome Endopeptidase Complex / metabolism
  • Viral Envelope Proteins / immunology*
  • Viral Envelope Proteins / metabolism*


  • ATP-Binding Cassette Transporters
  • Antigens, Viral
  • Epitopes, T-Lymphocyte
  • H-2 Antigens
  • H-2Kb protein, mouse
  • Viral Envelope Proteins
  • glycoprotein B, Simplexvirus
  • transporter associated with antigen processing (TAP)
  • Oxidoreductases
  • Ifi30 protein, mouse
  • Oxidoreductases Acting on Sulfur Group Donors
  • Proteasome Endopeptidase Complex