Molecular features of the hepatitis B virus nucleocapsid T‐cell epitope 18‐27: Interaction with HLA and T‐cell receptor

The strength of the cytotoxic T lymphocyte (CTL) response noma. 1,2 Interferons are the most effective available drugs for is believed to influence the final outcome of hepatitis B virus treatment of chronic HBV infection. However, a series of (HBV) infection. Among the different CTL epitopes so far problems are connected to the use of interferons and indicate identified, the sequence 18-27 of the HBV nucleocapsid anti- the need for defining alternative therapeutic approaches. gen is widely recognized by CTL of HLA-A2‐positive patients First, only about 20% of treated patients maintain a longwith acute self-limited HBV infection, and represents the main lasting response to interferon. Second, interferon treatment component of a peptide-based therapeutic vaccine aimed at is expensive and therefore not suited for developing world stimulating the antiviral CTL response in patients with areas, where HBV infection is unfortunately highly prevalent. chronic hepatitis B. In the present study, we further analyzed Finally, side effects can be severe, and a significant fraction the features of this important HBV region by the following: of chronic patients are not eligibile for treatment. 3 1) defining the contribution of individual residues of the epi- A better understanding of the immunopathogenesis of tope to the interaction with the T-cell receptor (TCR) and HBV infection and improvements in vaccine technology prowith the HLA-A0201 molecule; 2) assessing the antigenicity vide new tools to design more specific and rational treatments of this viral region in the context of the different HLA-A2 of HBV infection. A great deal of evidence suggests that both subtypes; and 3) testing whether this sequence can stimulate cellular and humoral responses are required for viral clearnot only HLA-class I but also HLA class II restricted T-cell ance. HBV-specific cytotoxic T lymphocytes (CTL) play a responses. A clear hierarchy was observed in the ability of crucial role in the control of the infection, 2 through direct individual residues to act as TCR or HLA binding sites. Fur- lysis of virus-infected cells and release of cytokines at the thermore, the sequence HBc18-27 was able to be recognized site of infection. 4 Indeed, patients who successfully recover by specific CTL when presented in the context of different from acute viral hepatitis develop strong and multispecific HLA-A2 subtypes. Finally, this HBV region was also found to HLA class I and class II restricted T-cell responses, 5-8 whereas stimulate HLA class II restricted T-cell responses. These data these responses are weak or absent in patients with chronic further increase the potential coverage and efficacy of thera- hepatitis B. 7,9,10 It follows that strategies aimed at boosting peutic vaccines based on the HBc18-27 sequence. (HEPATOL- the weak HBV-specific immune reactions typical of chronic