Modulation of TAP-dependent antigen compartmentalization during human monocyte-to-DC differentiation

Döring, Marius; Blees, Hanna; Koller, Nicole; Tischer-Zimmermann, Sabine; Müsken, Mathias; Henrich, Frederik; Becker, Stephan; Grabski, Elena; Wang, Junxi; Janssen, Hans; Zuschratter, Werner; Neefjes, Jacques; Klawonn, Frank; Tampé, Robert; Kalinke, Ulrich

doi:10.1182/bloodadvances.2018027268

Cited by 14 publications

(19 citation statements)

References 63 publications

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“…Simultaneously, lymphocyte costimulatory molecules (e.g. CD80, CD86) appear on the DC surface to activate the B and T cells [166][167][168][169]. The MHC class II-peptide and costimulatory proteins activate CD4 + T-helper cells and T-helper cells are required for both B and T cell proliferation and differentiation processes [170][171][172].…”

Section: Vlp-based Vaccine As An Inducer Of Adaptive Immunitymentioning

confidence: 99%

Virus-like particles: preparation, immunogenicity and their roles as nanovaccines and drug nanocarriers

et al. 2021

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Virus-like particles (VLPs) are virus-derived structures made up of one or more different molecules with the ability to self-assemble, mimicking the form and size of a virus particle but lacking the genetic material so they are not capable of infecting the host cell. Expression and self-assembly of the viral structural proteins can take place in various living or cell-free expression systems after which the viral structures can be assembled and reconstructed. VLPs are gaining in popularity in the field of preventive medicine and to date, a wide range of VLP-based candidate vaccines have been developed for immunization against various infectious agents, the latest of which is the vaccine against SARS-CoV-2, the efficacy of which is being evaluated. VLPs are highly immunogenic and are able to elicit both the antibody- and cell-mediated immune responses by pathways different from those elicited by conventional inactivated viral vaccines. However, there are still many challenges to this surface display system that need to be addressed in the future. VLPs that are classified as subunit vaccines are subdivided into enveloped and non- enveloped subtypes both of which are discussed in this review article. VLPs have also recently received attention for their successful applications in targeted drug delivery and for use in gene therapy. The development of more effective and targeted forms of VLP by modification of the surface of the particles in such a way that they can be introduced into specific cells or tissues or increase their half-life in the host is likely to expand their use in the future. Recent advances in the production and fabrication of VLPs including the exploration of different types of expression systems for their development, as well as their applications as vaccines in the prevention of infectious diseases and cancers resulting from their interaction with, and mechanism of activation of, the humoral and cellular immune systems are discussed in this review.

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Section: Vlp-based Vaccine As An Inducer Of Adaptive Immunitymentioning

confidence: 99%

Virus-like particles: preparation, immunogenicity and their roles as nanovaccines and drug nanocarriers

et al. 2021

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“…Data was recorded by a FACSCelesta (BD) and processed using FlowJo V10 software. Gating strategy for semi-permeabilized cells was adopted as previously described 48 . Significance of peptide accumulation was calculated by One-way ANOVA with Turkey’s multiple comparison test using GraphPad Prism 5.…”

Section: Methodsmentioning

confidence: 99%

Light control of the peptide-loading complex synchronizes antigen translocation and MHC I trafficking

et al. 2021

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Antigen presentation via major histocompatibility complex class I (MHC I) molecules is essential to mount an adaptive immune response against pathogens and cancerous cells. To this end, the transporter associated with antigen processing (TAP) delivers snippets of the cellular proteome, resulting from proteasomal degradation, into the ER lumen. After peptide loading and editing by the peptide-loading complex (PLC), stable peptide-MHC I complexes are released for cell surface presentation. Since the process of MHC I trafficking is poorly defined, we established an approach to control antigen presentation by introduction of a photo-caged amino acid in the catalytic ATP-binding site of TAP. By optical control, we initiate TAP-dependent antigen translocation, thus providing new insights into TAP function within the PLC and MHC I trafficking in living cells. Moreover, this versatile approach has the potential to be applied in the study of other cellular pathways controlled by P-loop ATP/GTPases.

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“…Binding of PAMPs (such as VLPs) to PRRs expressed on the DCs, including TLRs (2,131) and CLRs (28,131), prompt the maturation of DCs. During this process, peptide-MHC complexes are produced and lymphocyte costimulatory molecules are expressed on high quantity on the surface of DCs (6,143,144) including CD80, CD83, and CD86, which are necessary for efficient activation of effector B and T cells (4,44,144,145). As an example, incubation of immature DCs with HPV-16 VLPs induce overexpression of CD80 and CD83 and secretion of IL-12 (50), which is important for activating Th1 cells (146)(147)(148).…”

Section: Maturation Induced By Vlpsmentioning

confidence: 99%

Interaction Between Virus-Like Particles (VLPs) and Pattern Recognition Receptors (PRRs) From Dendritic Cells (DCs): Toward Better Engineering of VLPs

2020

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Virus-like particles (VLPs) have been shown to be strong activators of dendritic cells (DCs). DCs are the most potent antigen presenting cells (APCs) and their activation prompts the priming of immunity mediators based on B and T cells. The first step for the activation of DCs is the binding of VLPs to pattern recognition receptors (PRRs) on the surface of DCs, followed by VLP internalization. Like wild-type viruses, VLPs use specific PRRs from the DC; however, these recognition interactions between VLPs and PRRs from DCs have not been thoroughly reviewed. In this review, we focused on the interaction between proteins that form VLPs and PRRs from DCs. Several proteins that form VLP contain glycosylations that allow the direct interaction with PRRs sensing carbohydrates, prompting DC maturation and leading to the development of strong adaptive immune responses. We also discussed how the knowledge of the molecular interaction between VLPs and PRRs from DCs can lead to the smart design of VLPs, whether based on the fusion of foreign epitopes or their chemical conjugation, as well as other modifications that have been shown to induce a stronger adaptive immune response and protection against infectious pathogens of importance in human and veterinary medicine. Finally, we address the use of VLPs as tools against cancer and allergic diseases.

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Modulation of TAP-dependent antigen compartmentalization during human monocyte-to-DC differentiation

Cited by 14 publications

References 63 publications

Virus-like particles: preparation, immunogenicity and their roles as nanovaccines and drug nanocarriers

Virus-like particles: preparation, immunogenicity and their roles as nanovaccines and drug nanocarriers

Light control of the peptide-loading complex synchronizes antigen translocation and MHC I trafficking

Interaction Between Virus-Like Particles (VLPs) and Pattern Recognition Receptors (PRRs) From Dendritic Cells (DCs): Toward Better Engineering of VLPs

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