Comparison of cytotoxic T-lymphocyte responses to hepatitis C virus core protein in uninfected and infected individuals
- Resource Type
- Authors
- M, Jackson; B, Smith; D J, Bevitt; M, Steward; G L, Toms; M F, Bassendine; A G, Diamond
- Source
- Journal of medical virology. 58(3)
- Subject
- Epitopes
Viral Core Proteins
Histocompatibility Antigens Class I
Leukocytes, Mononuclear
Humans
Hepacivirus
Cytotoxicity Tests, Immunologic
Hepatitis C
T-Lymphocytes, Cytotoxic
- Language
- ISSN
- 0146-6615
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.