Immunoprevalence and Immunodominance of HLA-Cw0801- Restricted T Cell Response Targeting the Hepatitis B Virus Envelope Transmembrane Region

HLA-C-restricted T cells have been shown to play an important role in HIV control, but their impact on protection or pathogen-esis in other viral infections remains elusive. Here, we characterized the hierarchy of HLA class I-restricted hepatitis B virus (HBV) epitopes targeted by CD8 T cells in HBV-infected subjects. The frequency of CD8 T cells specific for a panel of 18 HBV epitopes (restricted by HLA-A0201/03/07 [hereinafter HLA-A0201/03/07],-A1101,-A2402/07,-B5801,-B4001,-B1301, and-Cw0801) was quantified in a total of 59 subjects who resolved HBV infection. We found that the HLA-Cw0801-restricted epitope comprised of Env residues 171 to 180 (Env171–180) is immunoprevalent in the Southeast Asian subjects (10/17 HLA-Cw0801-positive subjects) and immunodominant in the majority of HLA-Cw0801-positive subjects able to control HBV infec-tion. HLA-Cw0801-restricted Env171–180-specific CD8 T cells recognized endogenously produced HBV surface antigen (HBsAg) and tolerated amino acid variations within the epitope detected in HBV genotypes B and C. In conclusion, we demonstrate that the HLA-Cw0801-restricted Env171–180 T cell response is an important component of the HBV-specific adaptive T cell immunity in Asians infected with HBV. Thus, HLA-C restricted T cells might play an important role in various viral infections. During viral infections, CD8 T cells clear virus-infected cellsdue to their ability to recognize viral proteins presented, in the form of short peptides, by different major histocompatibility complex (MHC) class I molecules on the surface of the cells. Tw