A peptide derived from hepatitis C virus (HCV) core protein inducing cellular responses in patients with HCV with various HLA class IA alleles

Abstract

C35-44 peptide is a well known HLA-A2-restricted CTL epitope originating from hepatitis C virus (HCV) core protein. It was reported that the majority of HCV positive patients had significant levels of serum IgG specific to this peptide. This study addressed whether C35-44 peptide could induce CTL activity restricted to various HLA class IA alleles or could not. This peptide demonstrated binding activity to HLA-A*2402, -A*2601, -A*3101, and -A*3303 molecules, but not to HLA-A*1101 by means of stabilization assay. This peptide also induced CTL activity restricted to each of them, except HLA-A11(+) peripheral blood mononuclear cells from HCV 1b(+) patients by means of (51)Cr-release assay. With regard to HLA-A2 subtypes, this peptide demonstrated binding activity to HLA-A*0201 and -A*0206, but not to -A*0207 molecules. Furthermore, this peptide induced CTL activity from both the patients and healthy donors with all the HLA class IA molecules mentioned above by means of interferon-gamma production assay. These results may provide new insights for the development of a novel peptide vaccine against HCV compatible with various HLA class IA types.

Clinical features and major histocompatibility complex genes as potential susceptibility factors in pediatric immune thrombocytopenia

“…23 KIRs downregulate cytotoxic T-lymphocyte and NK-cell responses by binding to MHC class I molecules, thereby preventing lysis of target cells. Several epitopes recognized by cytotoxic T lymphocytes are HLA-A11 restricted, including peptides derived from human papillomavirus, 24 hepatitis C virus, 25,26 human immunodeficiency virus, 27e29 and Epstein-Barr virus. 30e32 HLA-DQ5 is associated with a number of autoimmune disorders, such as myasthenia gravis, 33 juvenile rheumatoid arthritis, 34e36 and other diseases.…”

Identification of peptides applicable as vaccines for HLA‐A26‐positive cancer patients

“…( 3,15–17 ) Results from our previous study indicated that a certain few peptides could bind to more than one type of HLA molecule. ( 2,3,18 )…”

“…RMA‐S cells (mouse lymphoma cell line deficient in transporter associated with antigen processing [TAP]) were maintained in RPMI‐1640 supplemented with 10% FCS. RMA‐S‐A*2601/human beta‐2‐microglobulin (hb2m) cells were established as described previously ( 2 ) and maintained in RPMI‐1640 supplemented with 10% FCS, 0.75 mg/mL of Geneticin (Calbiochem, Darmstadt, Germany), and 2 μg/mL of Puromycin (Calbiochem).…”

“…Recently, we reported that certain peptides could bind more than one type of HLA molecule and induce related cytotoxic T lymphocyte (CTL) responses. ( 2,3 ) Therefore, this study aimed to determine whether peptides currently under clinical trial as vaccines for HLA‐A2, ‐A24, and HLA‐A3 supertype–positive cancer patients could be applicable in HLA‐A26‐positive patients.…”

Immune Response of Cytotoxic T Lymphocytes and Possibility of Vaccine Development for Hepatitis C Virus Infection

“…Yutani has reported a phase I study of HCV vaccine in Japanese patients who were either nonresponders to IFN therapy ( n = 23) or had refused treatment ( n = 3). A peptide derived from the HCV core region amino acid residues 35–44 is capable of inducing cellular immune responses in many patients with different HLA class I-A alleles [70]. This peptide was used to develop a series of 6 vaccine injections that enhanced the peptide-specific peripheral CTL activity in 15 out of 25 patients and 12 vaccine injections that augmented peptide-specific IgG production [71].…”