Hepatitis B virus core antigen epitopes presented by HLA-A2 single-chain trimers induce functional epitope-specific CD8+ T-cell responses in HLA-A2.1/Kb transgenic mice.
The potency of CD8+ cytotoxic T lymphocyte (CTL) responses toward core antigen has been shown to affect the outcomes of hepatitis B virus (HBV) infection. Since single-chain trimers (SCT) composed of peptide epitope beta2-microglobulin (beta2m) and major histocompatibility complex (MHC) class I heavy chain covalently linked together in a single molecule have been shown to stimulate efficient CTL responses, we investigated the properties of human leucocyte antigen (HLA)-A2 SCTs encoding the HBV core antigen (HBcAg) epitopes C(18-27) and C(107-115). Transfection of NIH-3T3 cells with pcDNA3.0-SCT-C(18-27) and SCT-C(107-115) leads to stable presentation of HBcAg epitopes at the cell surface. HLA-A2.1/Kb transgenic mice vaccinated with the SCT constructs, either as a DNA vaccine alone or followed by a boost with recombinant vaccinia virus, were shown to generate HBcAg-specific CTL responses by enzyme-linked immunospot assay (ELISPOT) and in vitro interferon-gamma release experiments. HBcAg-specific CTLs from vaccinated HLA-A2.1/Kb transgenic mice were able to inhibit HBV surface and e antigen expression as indicated by HepG2.2.15 cells. Our data indicate that a DNA vaccine encoding a human HLA-A2 SCT with HBV epitopes can lead to stable, enhanced HBV core antigen presentation, and may be useful for the control of HBV infection in HLA-A2-positive HBV carriers.
Zhang
Yuxia
Y
Center for Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Li
Shu
S
Shan
Ming
M
Pan
Xuwen
X
Zhuang
Ke
K
He
Lihua
L
Gould
Keith
K
Tien
Po
P
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D006511:Hepatitis B Antigens / Q000096:biosynthesis; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D013154:Spleen / Q000276:immunology; D014162:Transfection; D019444:Vaccines, DNA / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology; D001613:beta 2-Microglobulin / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D006511:Hepatitis B Antigens; D006512:Hepatitis B Core Antigens; D017325:Hepatitis B Vaccines; D015395:Histocompatibility Antigens Class I; D019444:Vaccines, DNA; D001613:beta 2-Microglobulin