Characterization of T-cell responses against immunodominant epitopes from hepatitis C virus E2 and NS4a proteins.
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.
Sarobe
P
P
Division of Hepatology and Gene Therapy, Clínica Universitaria/School of Medicine, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain. psarobe@unav.es
Lasarte
J-J
JJ
García
N
N
Civeira
M P
MP
Borrás-Cuesta
F
F
Prieto
J
J
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D005260:Female; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology* / Q000821:virology; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007376:Interleukin-2 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D014759:Viral Envelope Proteins / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000276:immunology*
D006684:HLA-DR Antigens; D016056:Immunodominant Epitopes; D007376:Interleukin-2; C093542:NS4 protein, hepatitis C virus; D010446:Peptide Fragments; D012367:RNA, Viral; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; C091015:glycoprotein E2, Hepatitis C virus