Characterization of the specific CD4+ T cell response against the F protein during chronic hepatitis C virus infection

• Published in: PloS one 2010-12, Vol.5 (12), p.e14237-e14237
• Main Authors: Gao, De-Yong, Jin, Gen-Di, Yao, Bi-Lian, Zhang, Dong-Hua, Gu, Lei-Lei, Lu, Zhi-Meng, Gong, Qiming, Lone, Yu-Chun, Deng, Qiang, Zhang, Xin-Xin
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animal models; Animals; Antibodies; CD4 antigen; CD4-Positive T-Lymphocytes; CD4-Positive T-Lymphocytes - metabolism; Chronic infection; Deoxyribonucleic acid; DNA; DNA vaccines; Epitopes; Epitopes - chemistry; F protein; Gastroenterology and Hepatology/Hepatology; Genotyping; Hepacivirus; Hepacivirus - metabolism; Hepatitis; Hepatitis C; Hepatitis C - virology; Hepatitis C virus; Histocompatibility antigen HLA; HLA Antigens; HLA Antigens - metabolism; Humans; Immunology; Immunology/Immune Response; Immunopathogenesis; Infectious Diseases/Viral Infections; Interferon; Interferon-gamma; Interferon-gamma - metabolism; Leukocytes, Mononuclear; Leukocytes, Mononuclear - metabolism; Life Sciences; Liver; Lymphocytes T; Major histocompatibility complex; Mice; Mice, Transgenic; Microbiology and Parasitology; Molecular Sequence Data; Patients; Peptides; Peripheral blood mononuclear cells; Rodents; Spleen; Spleen - cytology; Transgenic mice; Vaccination; Viral Fusion Proteins; Viral Fusion Proteins - metabolism; Viral infections; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0014237

The hepatitis C virus (HCV) Alternate Reading Frame Protein (ARFP or F protein) presents a double-frame shift product of the HCV core gene. We and others have previously reported that the specific antibodies against the F protein could be raised in the sera of HCV chronically infected patients. However, the specific CD4(+) T cell responses against the F protein during HCV infection and the pathological implications remained unclear. In the current study, we screened the MHC class II-presenting epitopes of the F protein through HLA-transgenic mouse models and eventually validated the specific CD4(+) T cell responses in HCV chronically infected patients. DNA vaccination in HLA-DR1 and-DP4 transgenic mouse models, proliferation assay to test the F protein specific T cell response, genotyping of Chronic HCV patients and testing the F-peptide stimulated T cell response in the peripheral blood mononuclear cell (PBMC) by in vitro expansion and interferon (IFN)- γ intracellular staining. At least three peptides within HCV F protein were identified as HLA-DR or HLA-DP4 presenting epitopes by the proliferation assays in mouse models. Further study with human PBMCs evidenced the specific CD4(+) T cell responses against HCV F protein as well in patients chronically infected with HCV. The current study provided the evidence for the first time that HCV F protein could elicit specific CD4(+) T cell response, which may provide an insight into the immunopathogenesis during HCV chronic infection.