Antibody Reactive to a Hepatitis C Virus (HCV)‐Derived Peptide Capable of Inducing HLA‐A2 Restricted Cytotoxic T Lymphocytes Is Detectable in a Majority of HCV‐Infected Individuals without HLA‐A2 Restriction

Abstract

Hepatitis C virus (HCV) is a single‐strand RNA virus. Approximately 170 million people around the world are persistently infected and are at risk of liver cirrhosis or cancer. There is an urgent need to develop both therapeutic and diagnostic modalities of HCV. One approach to achieve these goals would be to determine highly immunodominant HCV peptides which are recognized by both cellular and humoral immunities. This study reports one such peptide, HCV‐core protein at positions 35–44, having HLA‐A2 binding motifs. IgG specific to this CTL‐epitope peptide is consistently detectable in a majority of the patients with HCV infection regardless of the different HLA types, different disease conditions, and different HCV‐genotypes tested. The sequence LPRR at positions 37–40 is considered to be the fine epitope recognized by the IgG. These results may provide new insights for the development of both therapeutic and diagnostic modalities of HCV at lower costs.

New Epitope Peptides Derived from Hepatitis C Virus (HCV) 2a Which Have the Capacity to Induce Cytotoxic T Lymphocytes in HLA‐A2+ HCV‐Infected Patients

“…Since HCV is a highly heterogeneous virus and, in some circumstances, even a single amino acid variation within CTL epitopes facilitates viral escape from host immunity (1,8), amino acid mutation in these individuals may be the most plausible explanation. We previously reported that the HCV1b 35-44 peptide induced specific CTLs from the PBMCs of HCV1b-infected patients (26). In this study, the HCV2a 35-44 peptide, which has the same amino acid sequence as HCV1b 35-44, was also found to be immunogenic in some patients, but the rate of successful CTL induction was less than 50%.…”

Serum levels of IgG to the peptide of HCV1b core at positions 35–44 correlated with persistent infection, while levels of IgG to the peptide of NS5A at positions 2132–2140 correlated with better prognosis in HCV-infected patients

“…The cross-reactivity of anti-C35 IgG was observed in the sera of HTLV-1 + patients, which could in part be due to the fact that the HTLV-1 envelope protein also possesses the same previously reported Wne epitomic sequence (LPRR) as the C35 peptide at positions 37-40 [17]. The HIV tat protein also shares Wve amino acids (PRRGP) with the C35 peptide at positions 38-42; furthermore, the HIV envelope protein shares Wve amino acids (RRGPR) with the C35 peptide at positions 39-43.…”

“…We recently found two unique Abs speciWc to HCV1b-derived peptides; one of these Abs was speciWc to the human leukocyte antigen (HLA)-A2-restricted CTL epitope peptide of the HCV1b core protein at positions 35-44 (anti-C35 Ab), and the other Ab was speciWc to the HLA-A24-restricted CTL epitope peptide of the NS5A protein at positions 2132-2140 (anti-NS5A2132 Ab) [17]. These two Abs were detected in a majority of a sample of patients with HCV + , regardless of diVerences in terms of their disease conditions, but the biological activities of these Abs remain unclear at the present time.…”

T cell infiltration and prognosis in HCC patients

“…These initial results were consistent with a protective effect against tumor growth of T cell-mediated immune response directed to HCC-associated antigens. This hypothesis has been subsequently corroborated by the identification of antigen-specific T cells (at tumor site and in periphery) in HCC patients, with specificity for different classes of tumor-associated antigens including cancer testis [9,10], self antigens as AFP and SART-1 [11,12], as well as viral epitopes [13,14].…”

“…These initial results were consistent with a protective effect against tumor growth of T cell-mediated immune response directed to HCC-associated antigens. This hypothesis has been subsequently corroborated by the identification of antigen-specific T cells (at tumor site and in periphery) in HCC patients, with specificity for different classes of tumor-associated antigens including cancer testis [9,10], self antigens as AFP and SART-1 [11,12], as well as viral epitopes [13,14].Two papers in this issue of the Journal [15,16] provide further evidence for the contrasting roles of the immune system in HCC. In the first study Unitt and co-workers show that lymphocyte infiltration of the tumor and a high CD4 + :CD8 + T cell ratio are associated with a reduced risk of tumor recurrence following liver transplantation.…”