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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(s) -
NeumannHaefelin Christoph,
Timm Jörg,
Schmidt Julia,
Kersting Nadine,
Fitzmaurice Karen,
OniangueNdza Cesar,
Kemper Michael N.,
Humphreys Isla,
McKiernan Susan,
Kelleher Dermot,
Lohmann Volker,
Bowness Paul,
Huzly Daniela,
Rosen Hugo R.,
Kim Arthur Y.,
Lauer Georg M.,
Allen Todd M.,
Barnes Eleanor,
Roggendorf Michael,
Blum Hubert E.,
Thimme Robert
Publication year - 2010
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.23275
Subject(s) - epitope , genotype , virology , biology , human leukocyte antigen , hepatitis c virus , cd8 , subdominant , virus , immunology , t cell , antigen , immune system , gene , genetics
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. (H EPATOLOGY 2010;51:54–62.)