Epitopes described in "Quantitative analysis of hepatitis C virus-specific CD8(+) T cells in peripheral blood and liver using peptide-MHC tetramers."

Article Authors:X S He; B Rehermann; F X López-Labrador; J Boisvert; R Cheung; J Mumm; H Wedemeyer; M Berenguer; T L Wright; M M Davis; H B Greenberg
Article Title:Quantitative analysis of hepatitis C virus-specific CD8(+) T cells in peripheral blood and liver using peptide-MHC tetramers.
Reference Detail
Reference ID:315544
Abstract:It is believed that the hepatitis C virus (HCV)-specific CD8(+) cytotoxic T lymphocytes (CTLs) play a role in the development of liver cell injury and in the clearance of the virus. To develop a direct binding assay for HCV-specific CTLs, we generated two peptide-MHC tetramers by using the recombinant HLA A2.1 molecule and A2-restricted T cell epitopes of the HCV NS3 protein. With these reagents we are able to detect specific CD8(+) cells in the blood of 15 of 20 HLA-A2(+), HCV-infected patients, at a frequency ranging from 0.01% to 1.2% of peripheral CD8(+) T cells. Phenotypic analysis of these specific cells indicated that there is a significant variation in the expression of the CD45 isoforms and CD27 in different patients. A 6-hour incubation of one patient's blood with NS3 peptides resulted in the activation of the epitope-specific CD8(+) cells, as indicated by their expression of CD69 and IFN-gamma. We also detected NS3-specific CD8(+) T cells in the intrahepatic lymphocyte population isolated from liver biopsies of two HCV-infected patients. The frequency of these specific CD8(+) cells in the liver was 1-2%, at least 30-fold higher than in the peripheral blood. All of the intrahepatic NS3-specific CD8(+) T cells were CD69(+), suggesting that they were activated CTLs. Direct quantitation and characterization of HCV-specific CTLs should extend our understanding of the immunopathogenesis and the mechanism of clearance or persistence of HCV.
Affiliations:Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. xiasong@leland.stanford.edu.
Reference Type:Literature
PubMed ID:10318946
Journal:Proc Natl Acad Sci U S A
Journal Volume:96
Article Pages:5692-7
Journal ISSN:0027-8424
Article Chemical List:Antigens, CD;Epitopes;HLA-A2 Antigen;NS3 protein, hepatitis C virus;Peptide Fragments;Recombinant Proteins;Viral Nonstructural Proteins
Article MeSH List:Antigens, CD(immunology); CD8-Positive T-Lymphocytes(immunology; virology); Epitopes(immunology); Flow Cytometry; HLA-A2 Antigen(immunology); Hepacivirus(immunology); Liver(virology); Major Histocompatibility Complex(immunology); Peptide Fragments(immunology); Recombinant Proteins(immunology); T-Lymphocytes, Cytotoxic(immunology; virology); Viral Nonstructural Proteins(immunology)
Article Comments:Data originally imported from the HLA Ligand Database (http://hlaligand.ouhsc.edu/)
Curation Last Updated:2015-07-24 20:01:55