Defective Cross-Presentation of Viral Antigens in GILT-Free Mice

Not GILT-Free Processing CD8 + T cells respond to infections by recognizing peptide antigens bound to major histocompatability complex class I (MHC class I) protein expressed on the surface of antigen-presenting cells (APCs). Because MHC class I can only present intracellular antigens, antigen cross-presentation is important for responses to viruses that do not directly infect APCs. Antigen cross-presentation occurs when APCs acquire antigens by phagocytosis of dying virally infected cells and present them to CD8 + T cells. After internalization, antigens must enter the cytosol for processing by the proteasome. Singh and Cresswell (p. 1394 ) now show that GILT (gamma-interferon–inducible lysosomal thiolreductase) is required for cross-presentation in mice of disulfide-containing viral antigens. In mice lacking GILT, the CD8 + T cell response to antigens derived from disulfide-rich proteins was substantially impaired after influenza A or herpes simplex virus 1 infection. Thus, cross-presentation of some antigens requires an early processing step prior to proteasomal degradation in the cytosol and subsequent MHC class I loading.