Comparison of cytotoxic T-lymphocyte responses to hepatitis C virus core protein in uninfected and infected individuals.
Cytotoxic T lymphocytes have been implicated in the control of hepatitis C virus (HCV) infection. Recognition by cytotoxic T lymphocytes of epitopes within HCV core protein has been defined previously by in vitro stimulation with synthetic peptides. The aim of this study has been to examine cytotoxic T-lymphocyte responses generated against peptides produced naturally following intracellular processing of viral protein. Antigen-specific cytotoxic T-lymphocyte lines were generated from both HCV uninfected and infected individuals by culturing CD8+ T cells with autologous dendritic cells loaded intracytoplasmically with recombinant HCV core protein. Analysis of the epitopes recognized by core protein-specific cytotoxic T lymphocytes used synthetic peptides that were selected based on their predicted binding to HLA-A*0201 molecules. Core protein-specific cytotoxic T lymphocytes derived from HCV uninfected and infected individuals were able to lyse autologous target cells pulsed with each of 5 predicted epitopes. Generation of HCV-specific cytotoxic T lymphocytes using dendritic cells as antigen presenting cells provides a method of comparing the potential repertoire of cytotoxic T-lymphocyte responses to the responses that occur in chronically infected individuals. No evidence of a qualitatively different response by patient cytotoxic T lymphocytes was apparent which might explain persistence of the virus.
Jackson
M
M
School of Microbiological, Immunological and Virological Sciences, University of Newcastle upon Tyne, United Kingdom.
Smith
B
B
Bevitt
D J
DJ
Steward
M
M
Toms
G L
GL
Bassendine
M F
MF
Diamond
A G
AG
D003601:Cytotoxicity Tests, Immunologic; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D014758:Viral Core Proteins / Q000737:chemistry / Q000276:immunology*
D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D014758:Viral Core Proteins