HLA-B27 has a dominant role in restricting strong CD8+ T cell responses and driving viral escape in hepatitis B virus infection

Important insights into the immunobiology of HIV and HCV infection have been derived from the study of protective HLA-B27 restricted CD8+ T cell responses in these two important human viral infections. Indeed, immunodominant HLA-B27 restricted CD8+ T cell epitopes have been identified in both infections. Viral escape from these two protective epitopes is the main mechanism of T cell failure in the few HLA-B27+ patients who have a less favourable outcome. In hepatitis B virus (HBV) infection, however, the role of HLA-B27 has not been addressed so far. In addition, in contrast to HIV and HCV, viral escape is thought not to play a major role in HBV persistence, a concept that has been primarily based on experimental findings obtained for HLA-A2. We therefore aimed to gain insights into the role of HLA-B27 in HBV infection, as well as the role of viral escape in this context. We identified for the first time five HBV-specific HLA-B27 restricted epitopes in an HLA-B27+ patient with acute HBV infection. Three of these epitopes were located in the polymerase gene. Importantly, one of the epitopes located in polymerase was also targeted in 5 out of 7 HLA-B27+ patients with chronic HBV infection. We also performed a nearly viral genome wide sequence analysis in the 7 HLA-B27+ and 10 HLA-B27- control patients with chronic HBV infection. Importantly, we found evidence for HLA-B27 driven T cell pressure within the HBV polymerase gene. In summary, we identified a dominant role of HLA-B27 in restricting strong CD8+ T cell responses in HBV infection. We also found evidence for HLA-B27 driven T cell pressure leading to viral escape. In conclusion, our data indicate that HLA-B27 has a dominant role in diverse human viral infections such as HIV, HCV, and HBV. They also indicate that viral escape may be an important mechanism of T cell failure not only against highly mutable RNA viruses such as HIV and HCV, but also against more conserved DNA viruses such as HBV.

HBV - HLA-B27 - T cell response - virale escape