title: Characterization of the specific CD4+ T cell response against the F protein during chronic hepatitis C virus infection.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: De-Yong
authors.initials: DY
authors.lastname: Gao
authors.forename: Gen-Di
authors.initials: GD
authors.lastname: Jin
authors.forename: Bi-Lian
authors.initials: BL
authors.lastname: Yao
authors.forename: Dong-Hua
authors.initials: DH
authors.lastname: Zhang
authors.forename: Lei-Lei
authors.initials: LL
authors.lastname: Gu
authors.forename: Zhi-Meng
authors.initials: ZM
authors.lastname: Lu
authors.forename: Qiming
authors.initials: Q
authors.lastname: Gong
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Lone
authors.forename: Qiang
authors.initials: Q
authors.lastname: Deng
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D000939:Epitopes / Q000737:chemistry; D006680:HLA Antigens / Q000378:metabolism; D016174:Hepacivirus / Q000378:metabolism*; D006526:Hepatitis C / Q000821:virology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D013154:Spleen / Q000166:cytology; D014760:Viral Fusion Proteins / Q000378:metabolism*
chemical_list: D000939:Epitopes; D006680:HLA Antigens; D014760:Viral Fusion Proteins; D007371:Interferon-gamma