T cell recognition of hepatitis B and C viral antigens

The outcome of hepatitis B and C heavily depends on the appropriate virus specific T cell response. Both CD8+ and CD4+ T lymphocytes do not recognize native viral proteins but processed peptides bound to MHC class I and class II, respectively. For therapeutical intervention aimed at T lymphocytes in chronic carriers as well as for the development of new vaccines, a precise identification of immunodominant epitopes, which can be recognized by a majority of patients, is necessary. Biological features of certain viral antigens have been partly characterized in animal models, but with the availability of modern molecular technology it is possible to extend these findings to the human system. The identification of anchor residues and motifs in peptides, which are essential for binding to certain MHC class I and class II molecules, allows the prediction of MHC allele-specific epitopes within viral proteins. By the use of synthetic peptides and vaccinia expression vectors, several epitopes for cytotoxic and helper T lymphocytes have been identified in HBV and HCV antigens. In HBV infection cytotoxic T lymphocytes recognize epitopes within the polymerase protein, the envelope protein and the nucleocapsid. In HCV cytotoxic epitopes have so far been identified within the nucleocapsid, E1, E2 and NS2. Since virus specific CD8+ T lymphocytes lyse virus infected cells in vitro and seem to play an important role for viral elimination in vivo, activation of virus specific effector cells may be achieved by immunizing chronically infected patients with the MHC-allele-specific peptides. Epitopes for CD4+ T lymphocytes have been demonstrated in the majority of HBV- and HCV-proteins. Different subsets of CD4+ T lymphocytes influence the course of infection by the production of lymphokines which either support antibody production by B cells or cellular antiviral effector mechanisms. In acute and chronic HBV infection the HBcAg/HBeAg-specific T cell response is closely correlated to viral elimination and the occurrence of anti-HBe- and anti-HBs antibodies. In HCV infection the CD4+ T cell response appears to be more heterogenous, and better functional characterization of the CD4+ response to immunodominant peptide epitopes in association with certain disease stages is required. Since T cell activation, the resulting effector functions and binding of the peptide to the HLA-molecule mainly depend on the peptide structure, viral mutations leading to amino acid changes may contribute to T cell non-responsiveness or an inappropriate T cell response.(ABSTRACT TRUNCATED AT 400 WORDS)