Gamma-interferon production in response to hepatitis B core protein and its synthetic peptides in patients with chronic hepatitis B virus infection.

The nucleocapsid of hepatitis B virus (HBV) is an efficient immunogen in activating T cells to produce interferon-gamma (IFN-gamma) in patients with chronic HBV infection. We investigated hepatitis B core antigen (HBcAg)-specific T cell recognition, which seems to be implicated in the pathogenesis of chronic liver disease. IFN-gamma production by peripheral-blood mononuclear cells of patients with chronic HBV infection [25 patients with chronic active hepatitis (CAH) and 14 asymptomatic carriers of HBV (ASCs)] was measured by an enzyme-linked immunosorbent assay. P19 polypeptide, which is derived from recombinant HBcAg particle (rHBcAg), increased IFN-gamma production in patients with CAH, but its effect was weaker than that of rHBcAg. P19 had no stimulating effect on T cells from ASCs. The fine specificity of T cell recognition of HBcAg was examined using 8 kinds of synthetic peptides. T cells from the patients who responded against P19 polypeptide recognized the sites within the common sequences of HBcAg and HBeAg (p72-90, P90-99, P108-122 and P126-146). These results suggest that HBcAg and P19 are cross-reactive at the T cell level, and that these T cells recognize the sites within the common sequences of HBcAg and HBeAg in HBV-infected patients.