Epitopes described in "Comprehensive analysis of CD8(+)-T-cell responses against hepatitis C virus reveals multiple unpredicted specificities."

Article Authors:Georg M Lauer; Kei Ouchi; Raymond T Chung; Tam N Nguyen; Cheryl L Day; Deborah R Purkis; Markus Reiser; Arthur Y Kim; Michaela Lucas; Paul Klenerman; Bruce D Walker
Article Title:Comprehensive analysis of CD8(+)-T-cell responses against hepatitis C virus reveals multiple unpredicted specificities.
Reference Detail
Reference ID:1002106
Abstract:The hepatitis C virus (HCV)-specific CD8(+)-T-cell response is thought to play a critical role in HCV infection. Studies of these responses have largely relied on the analysis of a small number of previously described or predicted HCV epitopes, mostly restricted by HLA A2. In order to determine the actual breadth and magnitude of CD8(+)-T-cell responses in the context of diverse HLA class I alleles, we performed a comprehensive analysis of responses to all expressed HCV proteins. By using a panel of 301 overlapping peptides, we analyzed peripheral blood mononuclear cells (PBMC) from a cohort of 14 anti-HCV-positive, HLA A2-positive individuals in an enzyme-linked immunospot assay. Only four subjects had detectable HLA A2-restricted responses in PBMC, and only 3 of 19 predicted A2 epitopes were targeted, all of which were confirmed by tetramer analysis. In contrast, 9 of 14 persons showed responses with more comprehensive analyses, with many responses directed against previously unreported epitopes. These results indicate that circulating HCV-specific CD8(+)-T-cell responses can be detected in PBMC in the majority of infected persons and that these responses are heterogeneous with no immunodominant epitopes consistently recognized. Since responses to epitopes restricted by single HLA alleles such as HLA A2 do not predict the overall response in an individual, more comprehensive approaches, as shown here, should facilitate definition of the role of the CD8(+)-T-cell response in HCV infection. Moreover, the low level or absence of responses to many predicted epitopes provides a rationale for immunotherapeutic interventions to broaden cytotoxic-T-lymphocyte recognition.
Affiliations:Partners AIDS Research Center, Infectious Disease Division, Gastrointestinal Unit, Massachusetts General HospitalHarvard Medical School, Boston, Massachusetts 02114, USA.
Reference Type:Literature
PubMed ID:12021343
Journal:J Virol
Journal Volume:76
Article Pages:6104-13
Journal ISSN:1098-5514
Article Chemical List:Epitopes, T-Lymphocyte;HLA-A2 Antigen;Hepatitis C Antigens;Peptide Fragments;Viral Proteins
Article MeSH List:CD8-Positive T-Lymphocytes(immunology); Enzyme-Linked Immunosorbent Assay; Epitopes, T-Lymphocyte; HLA-A2 Antigen; Hepacivirus(immunology); Hepatitis C(immunology; virology); Hepatitis C Antigens(immunology); Humans; Lymphocyte Activation; Peptide Fragments(chemical synthesis; immunology); Viral Proteins(immunology)
Curation Last Updated:2016-01-08 21:03:37