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DOI: 10.1055/s-0029-1241361
The protective effect of HLA-B27 in hepatitis C virus infection requires presence of a genotype-specific immunodominant CD8+ T cell epitope
Introduction: HLA-B27 is associated with protection in 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.
Aim: 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.
Methods: The epitope-specific CD8+ T cell response as well as viral sequences were analyzed in HLA-B27+ patients with acute or chronic HCV genotype 1 or 3a infection. In addition, the HLA-B27 frequency was determined in a large cohort of patients chronically infected with HCV genotype 1 or 3a.
Results: The genotype 3a peptide is 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 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 be explained by inter-genotype sequence diversity leading to the loss of the immunodominant HLA-B27 epitope in viral strains other than genotype 1. Our results demonstrate the central role of a single HLA-B27 restricted epitope specific CD8+ T cell response in mediating protection in HCV genotype 1 infection and the difficulty to develop T cell based vaccines across the boundary of genotypes.