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Defective Cross-Presentation of Viral Antigens in GILT-Free Mice
Reshma Singh and Peter Cresswell
New Series, Vol. 328, No. 5984 (11 June 2010), pp. 1394-1398
Published by: American Association for the Advancement of Science
Stable URL: http://www.jstor.org/stable/40656074
Page Count: 5
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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 CDe⁺ 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 crosspresentation 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.
Science © 2010 American Association for the Advancement of Science