title: Protective effect of human leukocyte antigen B27 in hepatitis C virus infection requires the presence of a genotype-specific immunodominant CD8+ T-cell epitope.
abstract: Human leukocyte antigen B27 (HLA-B27) is associated with protection in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection. This protective role is linked to single immunodominant HLA-B27-restricted CD8+ T-cell epitopes in both infections. In order to define the relative contribution of a specific HLA-B27-restricted epitope to the natural course of HCV infection, we compared the biological impact of the highly conserved HCV genotype 1 epitope, for which the protective role has been described, with the corresponding region in genotype 3 that differs in its sequence by three amino acid residues. The genotype 3a peptide was not recognized by CD8+ T cells specific for the genotype 1 peptide. Furthermore, patients with acute or chronic infection with HCV genotype 3a did not mount T-cell responses to this epitope region, and their autologous viral sequences showed no evidence of T-cell pressure. Finally, we found a significantly higher frequency of HLA-B27 positivity in patients with chronic HCV genotype 3a infection compared to genotype 1 infection, indicating that there is no protection by HLA-B27 in HCV genotype 3 infection.
  
  
  CONCLUSIONS
  Our data indicate that the protective effect of HLA-B27 is limited to HCV genotype 1 infection and does not expand to other genotypes such as genotype 3a. This can most likely be explained by intergenotype sequence diversity leading to the loss of the immunodominant HLA-B27 epitope in viral strains other than genotype 1. Our results underline the central role of a single HLA-B27-restricted epitope-specific CD8+ T-cell response in mediating protection in HCV genotype 1 infection.
authors.affiliation: Department of Medicine II, University of Freiburg, Germany.|Centre of Chronic Immunodeficiency (CCI), University of Freiburg, Germany.|Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Boston, MA.
authors.forename: Christoph
authors.initials: C
authors.lastname: Neumann-Haefelin
authors.affiliation: Department of Virology, University of Essen, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Timm
authors.affiliation: Department of Medicine II, University of Freiburg, Germany.|Centre of Chronic Immunodeficiency (CCI), University of Freiburg, Germany.|Faculty of Biology, University of Freiburg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Schmidt
authors.affiliation: Department of Medicine II, University of Freiburg, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Kersting
authors.affiliation: Trinity Centre for Health Sciences, St. James' Hospital, Dublin, Ireland.
authors.forename: Karen
authors.initials: K
authors.lastname: Fitzmaurice
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Boston, MA.
authors.forename: Cesar
authors.initials: C
authors.lastname: Oniangue-Ndza
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Boston, MA.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Kemper
authors.affiliation: Nuffield Department of Clinical Medicine, University of Oxford, UK.
authors.forename: Isla
authors.initials: I
authors.lastname: Humphreys
authors.affiliation: Trinity Centre for Health Sciences, St. James' Hospital, Dublin, Ireland.
authors.forename: Susan
authors.initials: S
authors.lastname: McKiernan
authors.affiliation: Trinity Centre for Health Sciences, St. James' Hospital, Dublin, Ireland.
authors.forename: Dermot
authors.initials: D
authors.lastname: Kelleher
authors.affiliation: Department of Molecular Virology, University of Heidelberg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Lohmann
authors.affiliation: Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Bowness
authors.affiliation: Department of Virology, University of Freiburg, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Huzly
authors.affiliation: Department of Medicine, University of Colorado Health Sciences, Denver, CO.
authors.forename: Hugo R
authors.initials: HR
authors.lastname: Rosen
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Boston, MA.
authors.forename: Arthur Y
authors.initials: AY
authors.lastname: Kim
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Boston, MA.
authors.forename: Georg M
authors.initials: GM
authors.lastname: Lauer
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Boston, MA.
authors.forename: Todd M
authors.initials: TM
authors.lastname: Allen
authors.affiliation: Nuffield Department of Clinical Medicine, University of Oxford, UK.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Barnes
authors.affiliation: Department of Virology, University of Essen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Roggendorf
authors.affiliation: Department of Medicine II, University of Freiburg, Germany.
authors.forename: Hubert E
authors.initials: HE
authors.lastname: Blum
authors.affiliation: Department of Medicine II, University of Freiburg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Thimme
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015796:HLA-B27 Antigen / Q000276:immunology*; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D015796:HLA-B27 Antigen; D016056:Immunodominant Epitopes