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

Science  11 Jun 2010:
Vol. 328, Issue 5984, pp. 1394-1398
DOI: 10.1126/science.1189176

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Abstract

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.

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