Methods

Four-digit HLA class I typing and viral sequence analyses were performed in 78 HLA-B^{鈦?/sup>27+ patients with chronic HCV genotype 1 infection. CD8+ T cell analyses were performed in a subset of patients. In addition, HLA/peptide affinity was compared for HLA-B鈦?/sup>27:02 and 05.}

Results

The NS5B₂₈₂₀ epitope is only restricted by the HLA-B^{鈦?/sup>27 subtype HLA-B鈦?/sup>27:02 (that is frequent in Mediterranean populations), but not by the prototype HLA-B鈦?/sup>27 subtype B鈦?/sup>27:05. Indeed, the epitope is very dominant in HLA-B鈦?/sup>27:02+ patients and is associated with viral escape mutations at the anchor position for HLA-binding in 12 out of 13 HLA-B鈦?/sup>27:02+ chronically infected patients.}

Conclusions

The NS5B₂₈₂₀ epitope is immunodominant in the context of HLA-B^{鈦?/sup>27:02, but is not restricted by other HLA-B鈦?/sup>27 subtypes. This finding suggests an important role of HLA subtypes in the restriction of HCV-specific CD8+ responses. With minor HLA subtypes covering up to 39% of specific populations, these findings may have important implications for the selection of epitopes for global vaccines.}