Successful clearance of hepatitis C virus (HCV)
infection has been associated with strong cellular immune responses against
viral antigens. However, although the magnitude of these responses is clearly important for viral eradication, more studies are needed to unravel the fine specificity of the protective anti-HCV immunity in infected patients. This was the aim of the present study. Overlapping
peptides spanning the sequence of HCV E2 and NS4a
proteins were used to stimulate T cells from patients with
chronic hepatitis C divided into three groups: naïve patients, patients who exhibited sustained response to
interferon (IFN)-alpha
therapy and patients who failed to respond to the treatment.
Interleukin-2 production by stimulated cells was measured in each case. Patients with sustained response to
therapy had stronger responses to E2
peptides than nonresponders, whereas naïve patients demonstrated intermediate reactivity. In the case of NS4a, responses against
peptides where similar in all groups of patients. Analysis of the
peptides recognized by T cells showed that responses were broad and heterogeneous, and some
immunodominant epitopes, preferentially recognized by patients exhibiting sustained response to treatment, were found. These results confirm the role of cellular immune responses in viral clearance, and stress the importance of
immunodominant regions within HCV
antigens. These viral sequences may represent valuable immunogens for preparation of therapeutic or prophylactic
vaccines.