Activation of a heterogeneous hepatitis B (HB) core and e antigen-specific CD4+ T-cell population during seroconversion to anti-HBe and anti-HBs in hepatitis B virus infection

Author:

Jung M C1,Diepolder H M1,Spengler U1,Wierenga E A1,Zachoval R1,Hoffmann R M1,Eichenlaub D1,Frösner G1,Will H1,Pape G R1

Affiliation:

1. Institute for Immunology, University of Munich, Germany.

Abstract

Overcoming hepatitis B virus infection essentially depends on the appropriate immune response of the infected host. Among the hepatitis B virus antigens, the core (HBcAg) and e (HBeAg) proteins appear highly immunogenic and induce important lymphocyte effector functions. In order to investigate the importance of HBcAg/HBeAg-specific T lymphocytes in patients with acute and chronic hepatitis B and to identify immunodominant epitopes within the HBcAg/HBeAg, CD4+ T-cell responses to hepatitis B virus-encoded HBcAg and HBcAg/HBeAg-derived peptides were studied in 49 patients with acute and 39 patients with chronic hepatitis B. The results show a frequent antigen-specific CD4+ T-cell activation during acute hepatitis B infection, a rare HBcAg/HBeAg-specific CD4+ T-cell response among HBeAg+ chronic carriers, and no response in patients with anti-HBe+ chronic hepatitis. An increasing CD4+ T-cell response to HBcAg/HBeAg coincides with loss of HBeAg and hepatitis B virus surface antigen (HBsAg). Functional analysis of peptide-specific CD4+ T-cell clones revealed a heterogeneous population with respect to lymphokine production. Epitope mapping within the HBcAg/HBeAg peptide defined amino acids (aa) 1 to 25 and aa 61 to 85, irrespective of the HLA haplotype, as the predominant CD4+ T-cell recognition sites. Other important sequences could be identified in the amino-terminal part of the protein, aa 21 to 45, aa 41 to 65, and aa 81 to 105. The immunodominant epitopes are expressed in both proteins, HBcAg and HBeAg. Our findings lead to the conclusion that activation of CD4+ T lymphocytes by HBcAg/HBeAg is a prerequisite for viral elimination, and further studies have to focus on the question of how to enhance or induce this type of T-cell response in chronic carriers. The immunodominant viral sequences identified may have relevance to synthetic vaccine design and to the use of peptide T-cell sites as immunotherapeutic agents in chronic infection.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

Reference30 articles.

1. HLA class-I human cytotoxic T cells recognize endogenously synthesized hepatitis B virus nucleocapsid antigen;Bertoletti A.;Proc. Natl. Acad. Sci. USA,1991

2. A functional dichotomy in CD4~ T;Bottomly K.;Iymphocytes. Immunol. Today,1988

3. Isolation of mononuclear cells and granulocytes from human blood;Böyum A.;Scand. J. Clin. Invest. Suppl.,1968

4. A TH1-TH2 switch is a critical step in the etiology of HIV infection;Clerici M.;Immunol. Today,1993

5. Diepolder H. M. M.-C. Jung R. Zachoval R. M. Hoffmann F. M. Zwiebel C. Korherr G. Paumgartner G. Riethmüller and G. R. Pape. 1994. Interferon-alpha (IFN) induced virus elimination in chronic hepatitis C: the role of virus-specific CD4~ T-lymphocytes in comparison to chronic hepatitis B abstr. 98. Presented at the International Meeting on Hepatitis C and Related Viruses.

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