Protective effect of human leukocyte antigen B27 in hepatitis C virus infection requires the presence of a genotype-specific immunodominant CD8+ T-cell epitope
✍ Scribed by Christoph Neumann-Haefelin; Jörg Timm; Julia Schmidt; Nadine Kersting; Karen Fitzmaurice; Cesar Oniangue-Ndza; Michael N. Kemper; Isla Humphreys; Susan McKiernan; Dermot Kelleher; Volker Lohmann; Paul Bowness; Daniela Huzly; Hugo R. Rosen; Arthur Y. Kim; Georg M. Lauer; Todd M. Allen; Eleanor Barnes; Michael Roggendorf; Hubert E. Blum; Robert Thimme
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 673 KB
- Volume
- 51
- Category
- Article
- ISSN
- 0270-9139
No coin nor oath required. For personal study only.
✦ Synopsis
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.