Diverging mechanisms of virus-specific CD8 T cell dysfunction result in protective versus pathogenic responses in chronic hepatitis B virus infection

Project Summary

The project will continue to investigate the diverging mechanisms of HBV-specific CD8+ T cell impairment linked to pathogenic versus protective immune responses in different clinical phases of chronic HBV infection (treatment-requiring chronic hepatitis B associated with liver damage versus inactive HBsAg carriers without liver pathology). Since the targeted antigen is a major determinant of HBV-specific CD8+ T cell impairment, HBV core- and HBV polymerase-specific CD8+ T cells will be considered separately. Ex vivo multi-omic approaches including single-cell RNA sequencing and ATAC sequencing, and in vitro cell culture models comprising genetic manipulation, activation and differentiation assays, will be applied to provide proof-of-principle analyses defining T cell-based targets to therapeutically improve HBV-specific CD8+ T cell function.