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 w ithin HCV core protein has been defined previously by in vitro stimulation with synthetic peptides. The aim of this study has been to examine cytotoxi c T-lymphocyte responses generated against peptides produced naturally foll owing intracellular processing of viral protein. Antigen-specific cytotoxic T-lymphocyte lines were generated from both HCV uninfected and infected in dividuals by culturing CD8(+) T cells with autologous dendritic cells loade d intracytoplasmically with recombinant HCV core protein. Analysis of the e pitopes recognized by core protein-specific cytotoxic T lymphocytes used sy nthetic peptides that were selected based on their predicted binding to HLA -A*0201 molecules. Core protein-specific cytotoxic T lymphocytes derived fr om HCV uninfected and infected individuals were able to lyse autologous tar get cells pulsed with each of 5 predicted epitopes. Generation of HCV-speci fic cytotoxic T lymphocytes using dendritic cells as antigen presenting cel ls provides a method of comparing the potential repertoire of cytotoxic T-l ymphocyte responses to the responses that occur in chronically infected ind ividuals. No evidence of a qualitatively different response by patient cyto toxic T lymphocytes was apparent which might explain persistence of the vir us. (C) 1999 Wiley-Liss, Inc.