MHC class II presentation of endogenously expressed antigens by transfected dendritic cells

Diebold, Sandra S.; Cotten, Matthew; Koch, Norbert; Zenke, Martin

doi:10.1038/sj.gt.3301433

Cited by 104 publications

(93 citation statements)

References 47 publications

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“…In these assays, macrophages transfected with constructs designed to secrete OVA were best for activating the DO11.10-GFP hybridoma, thus exogenous Ag may enter the MHC class II-processing pathway more efficiently than other Ag forms. Studies by others have also demonstrated the differing abilities of OVA targeted to different cellular locations of transfected DCs to stimulate proliferation of CD4 ϩ DO11.10 T cells (40). In these experiments, OVA targeted to the cell surface using the same TfR fusion construct used in our experiments, or as a fusion with murine invariant chain stimulated proliferation of T cells, whereas cytosolic Ag expression was ineffectual.…”

Section: Discussionmentioning

confidence: 62%

“…OVA expressed using this construct is secreted in mammalian cells (17). A plasmid expressing the transmembrane region of the human transferrin receptor (TfR) fused to aa 149 -385 from native OVA (plasmid expressing transferrin-OVA fusion protein; pTfROVA) has been described previously (39,40) and was kindly donated by M. Zenke (Max-Delbück-Center for Molecular Medicine, Berlin, Germany). This construct has been shown by others to target OVA expression to the surface of mammalian cells in vitro and in vivo (39,41).…”

Section: Plasmid Constructionmentioning

confidence: 99%

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Efficient Priming of CD4+ and CD8+ T Cells by DNA Vaccination Depends on Appropriate Targeting of Sufficient Levels of Immunologically Relevant Antigen to Appropriate Processing Pathways

Rush

Mitchell

Garside

2002

The Journal of Immunology

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The initial cellular events and interactions that occur following DNA immunization are likely to be key to determining the character and magnitude of the resulting immune response, and as such, a better understanding of these events could ultimately lead to the design of more effective pathogen-appropriate DNA vaccines. Therefore, we have used a variety of sensitive cell-based techniques to study the induction of adaptive immunity in vivo. We examined the efficacy of induction of Ag-specific CD4+ and CD8+ T cell responses in vivo by the adoptive transfer of fluorescently labeled Ag-specific TCR transgenic T cells and have demonstrated how such approaches can be used to study the effect of simple DNA construct manipulations on immunological priming. OVA-specific CD8+ and CD4+ T cells were activated and divided in vivo following immunization with DNA constructs that targeted OVA expression to different subcellular locations; however, the kinetics and degree of cell proliferation were dependent on the cellular location of the expressed protein. DNA vectors encoding cell-associated OVA resulted in greater CD8+ T cell division compared with other forms of OVA. In contrast, soluble secreted OVA targeted to the classical secretory pathway enhanced division of CD4+ T cells. Furthermore, the inclusion of mammalian introns to enhance protein expression increased the ability of poorly immunogenic forms of Ag to activate naive T cells, indicating that not only the location, but also the amount of Ag expression, is important for efficient T cell priming following DNA injection.

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Section: Discussionmentioning

confidence: 62%

Section: Plasmid Constructionmentioning

confidence: 99%

Efficient Priming of CD4+ and CD8+ T Cells by DNA Vaccination Depends on Appropriate Targeting of Sufficient Levels of Immunologically Relevant Antigen to Appropriate Processing Pathways

Rush

Mitchell

Garside

2002

The Journal of Immunology

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“…1 The primary advantage of a gene-based vaccination strategy using DCs transduced with the entire TAA gene is that the DCs will present multiple epitopes, including unknown epitopes associated with different MHC Class I molecules, in addition to helper epitopes associated with MHC Class II molecules. 23,24 Our study demonstrated that an adenovirus vector encoding the TAA gene, hgp100, can be used to effectively transfer and express the transgene in iPSDCs. On the other hand, it is generally accepted that iPS cells exhibit high efficiency and simplicity of transgene transfection using electroporation.…”

Section: Discussionmentioning

confidence: 74%

Antitumor immune response of dendritic cells (DCs) expressing tumor‐associated antigens derived from induced pluripotent stem cells: In comparison to bone marrow‐derived DCs

Iwamoto

Ojima

Hayata

et al. 2013

Intl Journal of Cancer

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It is generally accepted that the difficulty in obtaining a sufficient number of functional dendritic cells (DCs) is a serious problem in DC-based immunotherapy. Therefore, we used the induced pluripotent stem (iPS) cell-derived DCs (iPSDCs). If the therapeutic efficacy of iPSDCs is equivalent to that of bone marrow-derived DCs (BMDCs), then the aforementioned problems may be solved. In our study, we induced iPSDCs from iPS cells and examined the capacity for maturation of iPSDCs compared to that of BMDCs in addition to the capacity for migration of iPSDCs to regional lymph nodes. We adenovirally transduced the hgp100 gene, natural tumor antigens, into DCs and immunized mice once with the genetically modified DCs. The cytotoxic activity of CD8 (1) cytotoxic T lymphocytes (CTLs) was assayed using a 51 Cr-release assay. The therapeutic efficacy of the vaccination was examined in a subcutaneous tumor model. Our results showed that iPSDCs have an equal capacity to BMDCs in terms of maturation and migration. Furthermore, hgp100-specific CTLs were generated in mice immunized with genetically modified iPSDCs. These CTLs exhibited as high a level of cytotoxicity against B16 cells as BMDCs. Moreover, vaccination with the genetically modified iPSDCs achieved as high a level of therapeutic efficacy as vaccination with BMDCs. Our study clarified experimentally that genetically modified iPSDCs have an equal capacity to BMDCs in terms of tumor-associated antigenspecific therapeutic antitumor immunity. This vaccination strategy may therefore be useful for future clinical application as a cancer vaccine.

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“…Holst et al, 2008). A previous in vitro study (Diebold et al, 2001) revealed that a construct coding for Ii chain fused to a model antigen stimulated MHC class II-restricted but also class Irestricted T cells; furthermore, MHC class I presentation was more efficient. The present results seem to be in line with these observations, extending those results to the in vivo situation.…”

Section: Resultsmentioning

confidence: 99%

Fusion of a viral antigen to invariant chain leads to augmented T-cell immunity and improved protection in gene-gun DNA-vaccinated mice

Grujić

Holst

Christensen

et al. 2009

Journal of General Virology

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It has recently been demonstrated that a recombinant replication-deficient human adenovirus 5 (Ad5) vector expressing lymphocytic choriomeningitis virus (LCMV) glycoprotein (GP) fused to the p31 invariant (Ii) chain confers broad, long-lasting T-cell immunity that completely protects C57BL/6 mice against lethal peripheral challenge. The current study questioned whether the same strategy, i.e. linkage of GP to an Ii chain, could be applied to a naked DNA vaccine. Following gene-gun immunization with the linked construct (DNA-IiGP), GP-specific CD4 + T cells could not be detected by flow cytometry. However, inclusion of the Ii chain augmented the priming of GP-specific CD8 + T cells directed towards both immunodominant ) and subdominant (GP 276-286 and GP 92-101 ) epitopes, and vaccination with DNA-IiGP conferred significantly improved protection against systemic LCMV infection compared with the unlinked construct. In contrast, substantial protection against peripheral challenge was not observed. Additional experiments with T-cell subset-depleted or perforin-deficient mice revealed that virus control in vaccinated mice depends critically on cytotoxic CD8 + T cells. Finally, priming with the naked DNA vaccine was shown to augment the immune response raised by subsequent immunization with the Ad5 vector. In conclusion, this study showed that the immunoenhancing effect of Ii chain linkage is not limited to the Ad5 vector, but is also relevant with a DNA platform. Furthermore, given the fact that the Ii chain enhances the presentation of more than one epitope, this suggests that Ii-chain-based DNA vaccines may be promising candidates for various heterologous prime-boost regimes.

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MHC class II presentation of endogenously expressed antigens by transfected dendritic cells

Cited by 104 publications

References 47 publications

Efficient Priming of CD4+ and CD8+ T Cells by DNA Vaccination Depends on Appropriate Targeting of Sufficient Levels of Immunologically Relevant Antigen to Appropriate Processing Pathways

Efficient Priming of CD4+ and CD8+ T Cells by DNA Vaccination Depends on Appropriate Targeting of Sufficient Levels of Immunologically Relevant Antigen to Appropriate Processing Pathways

Antitumor immune response of dendritic cells (DCs) expressing tumor‐associated antigens derived from induced pluripotent stem cells: In comparison to bone marrow‐derived DCs

Fusion of a viral antigen to invariant chain leads to augmented T-cell immunity and improved protection in gene-gun DNA-vaccinated mice

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