The human cytomegalovirus US6 glycoprotein inhibits transporter associated with antigen processing-dependent peptide translocation

Proceedings of the National Academy of Sciences of the United States of America
P J LehnerP Cresswell

Abstract

In its attempt to evade cytotoxic T cell recognition, human cytomegalovirus encodes several genes that target MHC class I molecules at different points in their assembly pathway. We show here that the human cytomegalovirus US6 gene encodes a 22-kDa glycoprotein that binds the transporter-associated with antigen processing (TAP)/class I complex and inhibits translocation of peptide from the cytosol to the endoplasmic reticulum. Major histocompatibility complex class I molecules are therefore unable to load TAP-dependent peptides, resulting in the retention of MHC class I molecules in the endoplasmic reticulum, with a consequent reduction in class I at the cell surface. Interferon-gamma treatment of US6 transfected cells overcomes this inhibition of peptide translocation and restores class I at the cell surface to wild type levels. The functional consequence of TAP inhibition is that US6 transfected cells are unable to present endogenous antigen to cytotoxic T lymphocytes and are therefore resistant to cytotoxic T lymphocyte lysis.

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Citations

Jan 7, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·Y JunK Ahn
Apr 5, 2000·Nutrition Reviews·H L Ploegh
May 29, 2002·Proceedings of the National Academy of Sciences of the United States of America·Eddie C Y WangGavin W G Wilkinson
Oct 17, 2003·Proceedings of the National Academy of Sciences of the United States of America·Anne L AckermanPeter Cresswell
Apr 21, 2004·Immunology·Louise H BoyleJ S Hill Gaston
Dec 18, 2003·The Journal of Biological Chemistry·Joachim KochRobert Tampé
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