Dataset Information

Antigen Targeting of Porcine Skin DEC205⁺ Dendritic Cells.

ABSTRACT: Dendritic cell (DC) targeting by DEC205⁺ cells effectively promotes the internalization of antigens that may trigger a specific immune response. In this study, we evaluated the ability of a recombinant antibody, anti-DEC205 (rAb ZH9F7), to trigger cellular endocytosis in subpopulations of DCs and targeted cells after intradermal injection and subsequent migration toward lymph nodes. Furthermore, the cellular immune response was evaluated in pigs after intradermal application of the antigenized rAb ZH9F7 combined with porcine circovirus type 2 cap antigen (rAb ZH9F7-Cap). We demonstrated that rAb ZH9F7 recognized conventional type 1 and 2 DCs from the blood and skin and monocytes. It promoted receptor-mediated endocytosis and migration of cDCs and moDCs toward regional lymph nodes. Intradermal application of rAb ZH9F7-Cap induced a higher frequency of IFN-γ-secreting CD4⁺CD8⁺ T lymphocytes and antibodies against Cap protein than that in the control group. In conclusion, the rAb ZH9F7-Cap system promoted the target of skin cDC1 and cDC2, provoking migration to the regional lymph nodes and inducing a Th1 response, as evidenced by the proliferation of double-positive CD4⁺CD8⁺ T cells, which correlates with an enhanced ability to target the cDC1 subset both in vitro and in vivo.

SUBMITTER: Melgoza-Gonzalez EA

PROVIDER: S-EPMC9147619 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

Antigen Targeting of Porcine Skin DEC205<sup>+</sup> Dendritic Cells.

Melgoza-González Edgar Alonso EA Reséndiz-Sandoval Mónica M Hinojosa-Trujillo Diana D Hernández-Valenzuela Sofía S García-Vega Melissa M Mata-Haro Verónica V Tepale-Segura Araceli A Bonifaz Laura C LC Perez-Torres Armando A Hernández Jesús J

Vaccines 20220426 5

Dendritic cell (DC) targeting by DEC205<sup>+</sup> cells effectively promotes the internalization of antigens that may trigger a specific immune response. In this study, we evaluated the ability of a recombinant antibody, anti-DEC205 (rAb ZH9F7), to trigger cellular endocytosis in subpopulations of DCs and targeted cells after intradermal injection and subsequent migration toward lymph nodes. Furthermore, the cellular immune response was evaluated in pigs after intradermal application of the an ...[more]

PMID: 35632440

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Project description:Dendritic cells (DCs) are professional antigen-presenting cells that can recognize, capture, and process antigens. Fusing molecules targeting DCs with antigens can effectively improve the efficiency with which antigens are recognized and captured by DCs. This targeting strategy can be used for vaccine development to effectively improve the efficiency of antigen recognition and capture by DCs. The targeting sequence of porcine cytotoxic T-lymphocyte associated protein 4 (CTLA4), which binds porcine DCs, was identified in this study. Recombinant Lactobacillus reuteri (L. reuteri) expressing CTLA4-6aa (LYPPPY) and CTLA4-87aa fused to the porcine epidemic diarrhea virus (PEDV) protective antigen core neutralizing epitope (COE) were used to evaluate the ability of the two targeting motifs to bind the B7 molecule on DCs. Our results demonstrate that CTLA4-6aa could bind porcine DCs, and recombinant Lactobacillus expressing the CTLA4-6aa captured by porcine DCs was more efficient than those expressing CTLA4-87aa. In addition, the expression of DC markers, toll-like receptors, and cytokines was significantly higher in the 6aa-COE/L. reuteri-stimulated porcine DCs compared to DCs treated with 87aa-COE/L. reuteri (p<0.01) and recombinant Lactobacillus expressing CTLA4-6aa enhanced the ability of porcine DCs to activate T-cell proliferation. Our analysis of the protein structure revealed that CTLA4-87aa contains intramolecular hydrogen bonds, which may have weakened the intermolecular force between the residues on porcine CTLA4 and that on B7. In conclusion, recombinant Lactobacillus expressing CTLA4-6aa were more efficiently captured by porcine DCs and had a stronger ability to promote DC maturation and enhance T-cell proliferation. The LYPPPY motif is the optimal sequence for binding to porcine DCs. Piglets immunized with recombinant Lactobacillus showed that recombinant Lactobacillus expressing CTLA4-6aa induced significant levels of anti-PEDV-specific IgG and IgA antibody responses. Our study may promote research on DC-targeting strategies to enhance the effectiveness of porcine vaccines.

Dataset Information

Antigen Targeting of Porcine Skin DEC205⁺ Dendritic Cells.

Publications

Antigen Targeting of Porcine Skin DEC205<sup>+</sup> Dendritic Cells.

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Dataset Information

Antigen Targeting of Porcine Skin DEC205+ Dendritic Cells.

Publications

Antigen Targeting of Porcine Skin DEC205<sup>+</sup> Dendritic Cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Antigen Targeting of Porcine Skin DEC205⁺ Dendritic Cells.