PEPTIDES FOR INDUCTION OF IMMUNE RESPONSE BY CYTOTOXIC T LYMPHOCYTES AGAINST THE VIRUS OF HEPATITIS C

摘要

The hepatitis C virus (HCV) is the major cause of non-A, non-B vital hepatitis. The most striking feature of HCV induced liver disease is its tendency toward chronicity and slowly progressive liver cell injury. HLA Class I-restricted cytotoxic T lymphocyte (CTL) responses are considered to be a sine qua non for the effective clearance of vital infections. However, the characteristics of HCV-specific cytotoxic effector cells and identification of their cognate target antigens remains to be elucidated. This invention discloses novel HCV-derived peptides that are recognized by patient CTL. Peripheral blood mononuclear cells (PBMC) were obtained from HLA-A2 positive patients with chronic HCV infection and stimulated with HCV-derived peptides. Effector cells were tested for their ability to lyse HLA-A2-matched target cells sensitized either with a peptide or a vaccinia virus construct containing HCV sequences. Immunogenic HCV CTL peptides were identified in the putative core protein and nonstructural proteins (e.g., NS3-5). These peptides have the following amino acid sequences: ADLMGYIPLV (Core131-140), LLALLSCLTV (Core178-187), QLRRHIDLLV (E1257-266) , LLCPAGHAV (NS31169-1177), KLVALGINAV (NS31406-1415), SLMAFTAAV (NS41789-1797) , LLFNILGGWV (NS41807-1816), ILDSFDPLV (NS52252-2260), and DMLGYIPLV (Core132-140). These peptides facilitate the stimulation and identification of HCV-specific CTL and should provide useful diagnostic reagents for the detection of HCV infection.