title: Conserved hierarchy of helper T cell responses in a chimpanzee during primary and secondary hepatitis C virus infections.
abstract: Control of hepatitis C virus (HCV) infection could be influenced by the timing and magnitude of CD4+ T cell responses against individual epitopes. We characterized CD4+ T cells targeting seven Pan troglodytes (Patr) class II-restricted epitopes during primary and secondary HCV infections of a chimpanzee. All Patr-DR-restricted HCV epitopes bound multiple human HLA-DR molecules, indicating the potential for overlap in epitopes targeted by both species. Some human MHC class II molecules efficiently stimulated IL-2 production by chimpanzee virus-specific T cell clones. Moreover, one conserved epitope designated NS3(1248) (GYKVLVLNPSV) overlapped a helper epitope that is presented by multiple HLA-DR molecules in humans who spontaneously resolved HCV infection. Resolution of primary infection in the chimpanzee was associated with an initial wave of CD4+ T cells targeting a limited set of dominant epitopes including NS3(1248.) A second wave of low-frequency CD4+ T cells targeting other subdominant epitopes appeared in blood several weeks later after virus replication was mostly contained. During a second infection 7 years later, CD4+ T cells against all epitopes appeared in blood sooner and at higher frequencies but the pattern of dominance was conserved. In summary, primary HCV infection in this individual was characterized by T cell populations targeting two groups of MHC class II-restricted epitopes that differed in frequency and kinetics of appearance in blood. The hierarchial nature of the CD4+ T cell response, if broadly applicable to other HCV-infected chimpanzees and humans, could be a factor governing the outcome of HCV infection.
authors.affiliation: Center for Vaccines and Immunity, Columbus Children's Research Institute, 700 Children's Drive, Columbus, OH 43205, USA.
authors.forename: Naglaa H
authors.initials: NH
authors.lastname: Shoukry
authors.forename: John
authors.initials: J
authors.lastname: Sidney
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Walker
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002461:Cell Line, Transformed; D002999:Clone Cells; D017124:Conserved Sequence; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000097:blood / Q000276:immunology*; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology* / Q000821:virology; D015395:Histocompatibility Antigens Class I / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007117:Immunization, Secondary; D016056:Immunodominant Epitopes / Q000008:administration & dosage / Q000097:blood / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D010449:Peptide Mapping; D017386:Sequence Homology, Amino Acid; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000821:virology*; D014611:Vaccination; D017361:Viral Nonstructural Proteins / Q000276:immunology / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase
chemical_list: D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase