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A mutant HBs antigen (HBsAg)183–191 epitope elicits specific cytotoxic T lymphocytes in acute hepatitis B patients

HBs antigen (HBsAg)183–191 (FLLTRILTI, R187 peptide) is a dominant human leucocyte antigen‐A2 (HLA‐A2)‐restricted epitope associated with hepatitis B virus (HBV) infection in Caucasian populations. However, its prevalence is poorly understood in China, where there is a high incidence of HBV infection. In this report, we sequenced the region of HBsAg derived from 103 Chinese patients. Approximately 16·5% of the patients bore a mutant HBsAg183–191 epitope in which the original arginine (R187) was substituted with a lysine (K187 mutant peptide). Importantly, K187 still bound to HLA‐A2 with high affinity, and elicited specific cytotoxic T lymphocyte (CTL) responses in HLA‐A2/Kb transgenic mice. K187‐specific CTLs were also generated successfully in acute hepatitis B (AHB) patients, indicating that this mutant epitope is processed and presented effectively. Our findings show that R187‐specific CTLs can cross‐react with the K187 peptide. These findings reveal that K187 still has the property of an HLA‐A2 restricted epitope, and elicits a protective anti‐HBV CTL response in humans.