Inhibition of major histocompatibility complex Class I antigen presentation by hepatitis C virus core protein in myeloid dendritic cells.
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.
O'Beirne
James
J
Department of Liver Studies and Transplantation, Kings College London, Denmark Hill Campus, London SE59PJ, UK.
Mitchell
Jon
J
Farzaneh
Farzin
F
Harrison
Phillip M
PM
D000818:Animals; D017951:Antigen Presentation; D001854:Bone Marrow Cells / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D014162:Transfection; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology*
D015395:Histocompatibility Antigens Class I; C110366:OVA-8; D010446:Peptide Fragments; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D010047:Ovalbumin