CYTOTOXIC T-LYMPHOCYTE RESPONSE AND VIRAL LOAD IN HEPATITIS-C VIRUS-INFECTION

A cytotoxic T lymphocyte (CTL) response to the hepatitis C virus (HCV) nucleoprotein residues 88-96 that are the minimal and optimal epitope for human leukocyte antigen (HLA) B44-restricted CTLs was assessed in 27 HLA B44-positive patients with chronic HCV infection. Serum HCV RN A concentration and the amino acid sequence of the residues 81-100 wer e also determined. Three patients were infected with HCV with uncommon amino acid substitutions within the epitope. One was infected with HC V with an amino acid substitution in the flanking residues of the epit ope. To stimulate CTLs in the peripheral blood, 9-mer peptides that co rresponded to the residues 88-96 of the individual patients were synth esized and used. Seven of the 27 patients demonstrated a CTL response to the residues 88-96 with specific cytotoxic activities higher than 2 0%. The CTL activities were significantly higher in patients with a lo w titer of serum HCV RNA than in those with a high titer of serum HCV RNA (P = .0006). Some of the patients that demonstrated a CTL response to the residues 88-96 also demonstrated a CTL response to a newly ide ntified HLA B44-restricted CTL epitope or a known HLA All-restricted C TL epitope or both. No apparent association was observed between the C TL response and the stage of disease, or between the CTL response and the grade of necroinflammatory activity. The results suggest that the HLA B44-restricted CTLs together with other HCV-specific CTLs may inhi bit the outgrowth of HCV and that high-titer infection with HCV may su ppress the CTL responses.