PEPTIDE-SPECIFIC CTL INDUCTION IN HBV-SEROPOSITIVE PBMC BY STIMULATION WITH PEPTIDES IN-VITRO - NOVEL EPITOPES IDENTIFIED FROM CHRONIC CARRIERS

Cytotoxic T lymphocytes (CTL) recognize and destroy virus-infected cel ls, and it has been established that epitope-based peptides could indu ce such CTL in vivo as well as in vitro. In this study attempts were m ade to define the epitopes that are recognized by the CTL, and thus a series of 9- to 10-mer peptides derived from the amino acid sequences of hepatitis B virus (HBV) proteins were synthesized-on the basis of t he previously described HLA-A2 peptide binding motif. The binding assa y of the synthetic peptides using transporter-associated with antigen processing (TAP)-deficient human cell line, T2, showed that eight out of 11 peptides tested enhanced the expression of HLA-A2 molecules on t he T2 cell surface. Some of these peptides triggered activation of CTL in peripheral blood mononuclear cells of HBV-seropositive chronic car riers. The activated CTL in turn recognized and killed the T2 cells pu lsed with the same peptides. This study shows that novel HLA-A2-restri cted epitopes exist in the natural repertoire of immunity against HBV. These findings can be useful in developing peptide-based therapeutics against viral infections. (C) 1997 Elsevier Science B.V.