Similar as well as distinct MHC class I-binding peptides are generated by exogenous and endogenous processing of hepatitis B virus surface antigen

Schirmbeck, Reinhold; Wild, Jens; Reimann, Jörg

doi:10.1002/(sici)1521-4141(199812)28:12<4149::aid-immu4149>3.0.co;2-d

Cited by 64 publications

(63 citation statements)

References 32 publications

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“…It has been shown that in an inflammatory condition the constitutive proteasome is modified into immunoproteasome and that the epitope processing could be affected by either favoring or dampening epitope production (52). In addition, an alternative processing pathway is available for specific CTL induction by HBsAg, since exogenous envelope Ag can also enter the class I processing pathway and induce class I-restricted CTL (53,54). It was also shown that the alternative exogenous or the classical endogenous pathway may generate different peptides in mice (54).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, an alternative processing pathway is available for specific CTL induction by HBsAg, since exogenous envelope Ag can also enter the class I processing pathway and induce class I-restricted CTL (53,54). It was also shown that the alternative exogenous or the classical endogenous pathway may generate different peptides in mice (54). The processing of HBsAg secreted following natural infection or produced after DNA-based immunization could thus result in slightly different sets of epitopes.…”

Section: Discussionmentioning

confidence: 99%

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Multiepitopic HLA-A*0201-Restricted Immune Response Against Hepatitis B Surface Antigen After DNA-Based Immunization

Loirat

Lemonnier

Michel

2000

The Journal of Immunology

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CTL together with anti-envelope Abs represent major effectors for viral clearance during hepatitis B virus (HBV) infection. The induction of strong cytotoxic and Ab responses against the envelope proteins after DNA-based immunization has been proposed as a promising therapeutic approach to mediate viral clearance in chronically infected patients. Here, we studied the CTL responses against previously described hepatitis B surface Ag (HBsAg)-HLA-A*0201-restricted epitopes after DNA-based immunization in HLA-A*0201 transgenic mice. The animal model used was Human Human Db (HHD) mice, which are deficient for mouse MHC class I molecules (β2-microglobulin−/− Db−/−) and transgenic for a chimeric HLA-A*0201/Db molecule covalently bound to the human β2-microglobulin (HHD+/+). Immunization of these mice with a DNA vector encoding the small and the middle HBV envelope proteins carrying HBsAg induced CTL responses against several epitopes in each animal. This study performed on a large number of animals described dominant epitopes with specific CTL induced in all animals and others with a weaker frequency of recognition. These results confirmed the relevance of the HHD transgenic mouse model in the assessment of vaccine constructs for human use. Moreover, genetic immunization of HLA-A2 transgenic mice generates IFN-γ-secreting CD8+ T lymphocytes specific for endogenously processed peptides and with recognition specificities similar to those described during self-limited infection in humans. This suggests that responses induced by DNA immunization could have the same immune potential as those developing during natural HBV infection in human patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Multiepitopic HLA-A*0201-Restricted Immune Response Against Hepatitis B Surface Antigen After DNA-Based Immunization

Loirat

Lemonnier

Michel

2000

The Journal of Immunology

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“…Meanwhile, H-2 d mastocytome cells p815 were pulsed for 1 h at 37 ° C, 5% CO 2 in complete medium with 10 mmol/L S (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39) peptide IPQSLDSWWTSL from HBsAg. 33 After incubation p815 cells were further incubated for another 15 min with Mitomycin C (Sigma). The cells were extensively washed to avoid any trace of Mitomycin C and resuspended in complete medium for counting.…”

Section: Preparation Of Target and Effector Cellsmentioning

confidence: 99%

“…After washing, the cells were counted and distributed at 2 × 10 6 cells/mL in 10 mL RPMI FCS in 25 cm 2 flasks (Nalge-Nunc, Rochester, NY, USA) and stimulated with 10 mg/mL of peptide S (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39) . After culturing for 4 days in 5% CO 2 , half of the total medium was substituted and new medium containing 2 × 10 4 U/mL of IL-2 was added.…”

Section: In Vitro Re-stimulation Of Primed Ctlmentioning

confidence: 99%

Development of a nasal vaccine for chronic hepatitis B infection that uses the ability of hepatitis B core antigen to stimulate a strong Th1 response against hepatitis B surface antigen

et al. 2004

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SummaryThere are estimated to be 350 million chronic carriers of hepatitis B infection worldwide. Patients with chronic hepatitis B are at risk of liver cirrhosis with associated mortality because of hepatocellular carcinoma and other complications. An important goal, therefore, is the development of an effective therapeutic vaccine against chronic hepatitis B virus (HBV). A major barrier to the development of such a vaccine is the impaired immune response to HBV antigens observed in the T cells of affected patients. One strategy to overcome these barriers is to activate mucosal T cells through the use of nasal vaccination because this may overcome the systemic immune downregulation that results from HBV infection. In addition, it may be beneficial to present additional HBV epitopes beyond those contained in the traditional hepatitis B surface antigen (HbsAg) vaccine, for example, by using the hepatitis B core antigen (HBcAg). This is advantageous because HBcAg has a unique ability to act as a potent Th1 adjuvant to HbsAg, while also serving as an immunogenic target. In this study we describe the effect of coadministration of HBsAg and HBcAg as part of a strategy to develop a more potent and effective HBV therapeutic vaccine.

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“…Specific cytolytic activity of cells was tested in short-term 51 Cr-release assays against RBL5, RBL5/BMG (transfected with the BMGneo vector without insert), or RBL5/S transfectants (carrying the HBsAg-encoding BMGneo vector) (23). After a 3.5-h incubation at 37°C, 50 l of supernatant was collected for gamma-radiation counting.…”

Section: Hbsag-specific Ctlmentioning

confidence: 99%

Ongoing Murine T1 or T2 Immune Responses to the Hepatitis B Surface Antigen Are Excluded from the Liver that Expresses Transgene-Encoded Hepatitis B Surface Antigen

Schirmbeck

Wild

Stober

et al. 2000

The Journal of Immunology

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Different protein- or DNA-based vaccination techniques are available that prime potent humoral and cellular, T1 or T2 immune responses to the hepatitis B surface Ag (HBsAg) in mice. T1 and T2 are immune responses with isotype profile indicating Th1 and Th2 immunoregulation. We tested whether HBsAg-specific immune responses can be established in transgenic mice that express HBsAg in the liver (HBs-tg mice) using either these different vaccination techniques or an adoptive transfer system. HBsAg-specific responses could not be primed in HBs-tg mice with the established, potent vaccine delivery techniques. In contrast, adoptive transfers of T1- and T2-type HBsAg-immune spleen cells into congenic HBs-tg hosts (that were not conditioned by pretreatment) suppressed HBsAg antigenemia and gave rise to HBsAg-specific serum Ab titers. The establishment of continuously rising anti-HBsAg serum Ab levels with alternative isotype profiles (reflecting T1 or T2 polarization) in transplanted HBs-tg hosts required donor CD4+ T cell-dependent restimulation of adoptively transferred immune cells by transgene-derived HBsAg. Injections of HBsAg-specific Abs into HBs-tg mice did not establish stable humoral immunity. The expanding T1 or T2 immune responses to HBsAg in HBs-tg hosts did not suppress transgene-directed HBsAg expression in the liver and did not induce liver injury. In addition to priming functional antiviral effector cells, the conditioning of the liver microenvironment to enable delivery of antiviral effector functions to this organ are therefore critical for effective antiviral defense. A major challenge in the development of a therapeutic vaccine against chronic hepatitis B or C virus infection is thus the efficient targeting of specifically induced immune effector specificities to the liver.

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Similar as well as distinct MHC class I-binding peptides are generated by exogenous and endogenous processing of hepatitis B virus surface antigen

Cited by 64 publications

References 32 publications

Multiepitopic HLA-A*0201-Restricted Immune Response Against Hepatitis B Surface Antigen After DNA-Based Immunization

Multiepitopic HLA-A*0201-Restricted Immune Response Against Hepatitis B Surface Antigen After DNA-Based Immunization

Development of a nasal vaccine for chronic hepatitis B infection that uses the ability of hepatitis B core antigen to stimulate a strong Th1 response against hepatitis B surface antigen

Ongoing Murine T1 or T2 Immune Responses to the Hepatitis B Surface Antigen Are Excluded from the Liver that Expresses Transgene-Encoded Hepatitis B Surface Antigen

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