Characterization of an immunologically conserved epitope from hepatitis C virus E2 glycoprotein recognized by HLA-A2 restricted cytotoxic T lymphocytes.
OBJECTIVE
Identification of epitopes recognized by cytotoxic T lymphocytes (CTL) in hepatitis C virus (HCV) proteins is of importance because they can be used for vaccination, treatment of infection or monitoring of immune responses. Our purpose was to characterize new CTL epitopes in HCV structural proteins.


METHODS
Peptides were synthesized and tested in HLA-A2 binding assays. Binder peptides were used to stimulate peripheral blood mononuclear cells from HCV+ patients and controls, and activity measured in chromium release and ELISPOT assays.


RESULTS
Twenty binder peptides were found, and stimulation of HCV+ patient cells with nine peptides showing high binding ability led to the growth of CD8+ CTL recognizing peptide E2(614-622) in association with HLA-A2. Peptide E2(614-622) was recognized by 30% of HLA-A2+ patients with chronic HCV infection, but no responses were observed in control groups. Five peptides derived from region E2(614-622) from 26 different viral isolates bound to HLA-A2 molecules, and all of them but one, containing Phe at position 622, were recognized by E2(614-622) specific CTL.


CONCLUSIONS
These results show that peptide E2(614-622) belongs to a highly conserved region of HCV E2, and might be a good candidate to induce anti-HCV CTL responses in HLA-A2+ subjects.
Department of Internal Medicine, Medical School and University Clinic, University of Navarra, Pamplona, Spain. psarobe@unav.es
P
P
Sarobe
E
E
Huarte
J J
JJ
Lasarte
A
A
López-Díaz de Cerio
N
N
García
F
F
Borrás-Cuesta
J
J
Prieto
D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D017124:Conserved Sequence; D000939:Epitopes / Q000235:genetics / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000378:metabolism*; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D011485:Protein Binding; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D000956:Antigens, Viral; D000939:Epitopes; D015789:HLA-A2 Antigen; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus