MAPPING OF THE CELLULAR IMMUNE-RESPONSES TO WOODCHUCK HEPATITIS CORE ANTIGEN EPITOPES IN CHRONICALLY INFECTED WOODCHUCKS

T-cell responses to hepatitis B virus nucleocapsid antigens (HBcAg and HBeAg) play an important role in disease outcome in those infected wi th hepatitis B virus (HBV). The woodchuck is naturally infected in the wild with woodchuck hepatitis virus (WHV), which shows a high degree of genetic homology to HBV and produces a similar pattern of infection in its natural host. Twenty-three overlapping peptides were construct ed to cover the entire WHV core region and used to identify immunodomi nant cellular epitopes in the nucleocapsid antigen using peripheral bl ood lymphocytes from 12 chronic WHV carrier and 4 uninfected control a nimals. A peripheral blood lymphocyte response was seen in all of the chronic WHV carrier animals to at least one peptide, and in 8 of the 1 2 chronic carrier animals a response was observed to 5 common peptides : peptide analogues of amino acids 16-30, 38-52, 50-69, 76-90 and 91-1 05. Peptide 91-105 produced maximal proliferation in 5 out of 12 infec ted animals. In addition, a difference in response was observed betwee n wild and laboratory infected animals; the latter appeared to have a lower response to peptides than animals infected in the wild. This stu dy provides evidence that the woodchuck has a population of peripheral blood cells which are sensitised to epitopes within the nucleocapsid protein and provides a basis on which to develop the use of the woodch uck as an immunological model of HBV infection for testing therapeutic means of enhancing this response. (C) 1997 Wiley-Liss, Inc.