Mutation “Hot Spot” in HLA Class I-Restricted T Cell Epitope on Hepatitis B Surface Antigen in Chronic Carriers and Hepatocellular Carcinoma

Abstract

Mutations in the human hepatitis B virus (HBV) genome contribute to its escape from host immune surveillance and result in persistent infection. We report the identification of frequent mutations encompassing residues 29 to 53 of the HBV surface antigen in chronic HBV carriers as well as in patients with hepatocellular carcinoma. The location of these mutations, not found in patients with acute hepatitis and vaccinated infants, coincides with a human leukocyte antigen class I-restricted cytotoxic T lymphocyte epitope. Significantly, mutations occur at a higher frequency (83%) compared with those identified on the immunogenic “a” determinant (25%) of the corresponding patients. Our findings therefore suggest the potential importance of this novel mutation “hot spot” in the establishment of chronic HBV infection.