Summary auto-generated
This study identified a cytotoxic T lymphocyte (CTL) epitope of hepatitis C virus presented by HLA-B*3501 using reverse immunogenetics. Researchers synthesized 53 HCV peptides based on HLA-B*3501 binding motifs and tested their ability to induce CTL responses in blood cells from an HLA-B35-positive patient with acute hepatitis C. Twenty-eight peptides bound HLA-B*3501, and six induced specific CTL responses. The peptide HPNIEEVAL (HCV-B35-38) from the NS3 region was confirmed as a true epitope through CTL clone generation and vaccinia virus infection experiments. The epitope sequence was detected in virus isolates from the patient. Strong CTL responses to this epitope were observed during acute hepatitis C but disappeared during recovery. Importantly, CTL specific for this epitope could not be induced from patients with chronic hepatitis C, suggesting this epitope plays a crucial role in viral elimination during acute infection. These findings indicate CTL responses are important for clearing HCV in acute infection.
Key findings
- The HPNIEEVAL peptide (HCV-B35-38) was identified as an HLA-B*3501-restricted CTL epitope found in the NS3 region of hepatitis C virus
- This epitope induced strong CTL responses during acute hepatitis C infection but not during recovery or in patients with chronic hepatitis C
- The epitope sequence was naturally present in the patient's viral isolates and was processed and presented during infection as demonstrated by vaccinia virus experiments
- CTL response to this epitope appears critical for viral elimination, as it was detected only in the acute phase and absent in chronic infection
- Mutations in the epitope, particularly at anchor residue positions, reduced HLA-B*3501 binding and CTL recognition, explaining epitope escape in some viral strains
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Abstract
In order to clarify the role of cytotoxic T lymphocytes (CTL) in hepatitis C virus (HCV) infection, an HLA-B35-restricted cytotoxic T cell epitope of HCV was identified using a strategy called reverse immunogenetics. Twenty-eight of 53 HCV peptides carrying two anchor residues were selected as HLA-B*3501 binding peptides. These peptides were used to induce the specific cytotoxic T cells in peripheral blood lymphocytes from a patient with acute hepatitis C. Six HLA-B*3501 binding peptides induced the peptide-specific CTL. One (HPNIEEVAL) of five peptides was confirmed as the epitope by the specific T cell clones. A sequence identical to the epitope was detected in isolates of the virus from the patient and a strong CTL response to this epitope was observed in the acute phase of hepatitis C but not in the recovery phase. The specific CTL for this epitope were not detected in peripheral blood lymphocytes from patients with chronic hepatitis C. Together these results suggest that the CTL specific for this epitope have an important role in the elimination of the virus in the patient.