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Hepatology. 2010 Jan;51(1):54-62. doi: 10.1002/hep.23275.

Protective effect of human leukocyte antigen B27 in hepatitis C virus infection requires the presence of a genotype-specific immunodominant CD8+ T-cell epitope.

Author information

1
Department of Medicine II, University of Freiburg, Germany.
2
Centre of Chronic Immunodeficiency (CCI), University of Freiburg, Germany.
3
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Boston, MA.
4
Department of Virology, University of Essen, Germany.
5
Faculty of Biology, University of Freiburg, Germany.
6
Trinity Centre for Health Sciences, St. James' Hospital, Dublin, Ireland.
7
Nuffield Department of Clinical Medicine, University of Oxford, UK.
8
Department of Molecular Virology, University of Heidelberg, Germany.
9
Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
10
Department of Virology, University of Freiburg, Germany.
11
Department of Medicine, University of Colorado Health Sciences, Denver, CO.
#
Contributed equally

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.

CONCLUSION:

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.

PMID:
20034048
PMCID:
PMC4396188
DOI:
10.1002/hep.23275
[Indexed for MEDLINE]
Free PMC Article

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