In vivo hierarchy of immunodominant and subdominant HLA-A*0201-restricted T-cell epitopes of HBx antigen of hepatitis B virus.

Abstract

A polyepitopic CD8+ T-cell response is critical for the control of hepatitis B virus (HBV) infection. The HBV X protein (HBx) is a multifunctional protein that is important for the viral life cycle and for host-virus interactions. The aim of this study was to analyze the immunogenicity and dominance of various HLA-A*0201-restricted HBx-derived epitopes. For this purpose, we immunized HLA-A*0201-transgenic mice with HBx-derived peptides and DNA. This is a powerful model for studying the induction of HLA-A*0201-restricted immune responses in vivo, as these mice possess a cytotoxic T lymphocyte (CTL) repertoire representative of HLA-A2.1 individuals. We used cytotoxic tests and enzyme-linked immunosorbent spot (ELISPOT) assays to study the induction of specific cytotoxic and interferon (IFN)-gamma-secreting T cells. This allowed us to classify the HBx epitopes according to their T-cell activation capacity. After endogenous processing of the antigen synthesized in vivo after DNA-based immunization, we found that the HBx-specific T-cell response is targeted against one immunodominant epitope. Furthermore, following peptide immunization, we identified six additional novel subdominant T-cell epitopes. Inclusion of well-characterized epitopic sequences of HBx in a new vaccine for chronic HBV infections could help to broaden the T-cell response.

• Authors: Silvina Malmassari, Yu Chun Lone, Menghua Zhang, Catherine Transy, Marie-Louise Michel
• Journal: Microbes and infection (Microbes Infect) Vol. 7 Issue 4 Pg. 626-34 (Apr 2005) ISSN: 1286-4579 [Print] France
• PMID: 15820153 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Viral
• Epitopes, T-Lymphocyte
• HLA-A Antigens
• HLA-A*02:01 antigen
• HLA-A2 Antigen
• Immunodominant Epitopes
• Peptides
• Trans-Activators
• Viral Regulatory and Accessory Proteins
• hepatitis B virus X protein
• Interferon-gamma

Topics

• Amino Acid Sequence
• Animals
• DNA, Viral (administration & dosage, immunology)
• Epitopes, T-Lymphocyte (chemistry, immunology)
• Female
• HLA-A Antigens (metabolism)
• HLA-A2 Antigen
• Hepatitis B virus (immunology)
• Immunization
• Immunodominant Epitopes (immunology)
• Interferon-gamma (metabolism)
• Lymphocyte Activation
• Mice
• Mice, Transgenic
• Molecular Sequence Data
• Peptides (administration & dosage, chemistry, immunology)
• Plasmids (administration & dosage)
• T-Lymphocytes, Cytotoxic (immunology)
• Trans-Activators (chemistry, genetics, immunology)
• Viral Regulatory and Accessory Proteins