The cellular immune response to nucleocapsid antigens in hepatitis B virus infection

Mario U. Mondelli, Francis V. Chisari, Carlo Ferrari

Research output: Contribution to journalArticlepeer-review


The pathogenesis of HBV-induced hepatocellular injury still remains unsolved despite several years of continuous research effort by a number of investigators. A plausible hypothesis is shown in Fig. 1. The central issue is the role of CTL in causing liver cell death and HBV clearance. Although the HBV nucleoprotein has been suggested to be a major target antigen for CTL [16], it is entirely possible that selected regions of the viral envelope and other nonstructural proteins such as the polymerase may serve as target structure for HLA class I- or class II-restricted CTL recognition, as has been shown in other viral systems. CTL might in turn be negatively modulated by antibody masking of target antigen(s) [22] and by specific intrahepatic suppressor T cells which have been recently demonstrated to be active in chronic HBV infection [4]. In addition, helper T lymphocytes may exert an indirect cytotoxic effect through the release of cytokines such as tumor necrosis factor [5]. This circuit can be potentially amplified by soluble factor(s) secreted by autoreactive cells [5]. Finally, antibody-dependent cell-mediated cytotoxicity (ADCC) may also be a determinant of liver cell necrosis as has been suggested earlier [12]. The use of molecular vectors and of synthetic peptides derived from the various viral protein sequences will help us to dissect the immune response to HBV. We anticipate that this strategy will permit us to identify the function, phenotype, HLA restriction and antigenic fine specificity of HBV-specific CTL in HBV infection with the hope that such knowledge may ultimately be translated into more specific and effective therapeutic strategies for eradication of persistent HBV infection and associated liver disease in the future.

Original languageEnglish
Pages (from-to)25-31
Number of pages7
JournalSpringer Seminars in Immunopathology
Issue number1
Publication statusPublished - May 1990

ASJC Scopus subject areas

  • Immunology


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