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Virology. 2009 Jun 20;389(1-2):1-7. doi: 10.1016/j.virol.2009.03.035. Epub 2009 May 5.

Inhibition of major histocompatibility complex Class I antigen presentation by hepatitis C virus core protein in myeloid dendritic cells.

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  • 1Department of Liver Studies and Transplantation, Kings College London, Denmark Hill Campus, London SE59PJ, UK.

Abstract

Hepatitis C virus core (HCVcore) protein was expressed in myeloid dendritic cells (DC) from C57/B6 mice (H-2K(b)) by electroporation of HCVcore mRNA to investigate its effect on the ability of DC to prime CD8+ T cells displaying a T cell receptor specific for OVA(257-264) peptide (SIINFEKL)/H-2K(b) complex. Expression of full length HCVcore(191), which is directed to the endoplasmic reticulum (ER) membrane by a C-terminal signal sequence, but not a truncated variant HCVcore(152), which has a wider subcellular localization including the nucleus, significantly reduced surface levels of the H-2K(b)/SIINFEKL complex and impaired the ability of DC to prime naïve CD8+ T cells when they had to process endogenous antigen but not when MHC class I molecules were loaded directly with SIINFEKL peptide. Exploitation of the MHC class I antigen-processing pathway by HCVcore(191) impairs the ability of DC to stimulate CD8+ T cells and may contribute to the persistence of HCV infection.

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