Hepatitis B virus-like particles access major histocompatibility class I and II antigen presentation pathways in primary dendritic cells

Moffat, Jessica M; Cheong, Wan Shoo; Villadangos, José A; Mintern, Justine D.; Netter, Hans Jürgen

doi:10.1016/j.vaccine.2013.02.042

Cited by 23 publications

(19 citation statements)

References 41 publications

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“…Murine dendritic cells DC were isolated from spleens as previously described. 48 In brief, spleens were digested with DNase (Roche Applied Science, 10104159001) and type 3 collagenase (Worthington Biochemicals, CLS3) and enriched for light density cells by centrifugation in 1.077 g/cm3 Nycodenz (Progen Biotechnik, 1002424). DC were isolated after depletion using antibodies (generated in house) against CD3 (clone KT3-1.1), THY1 (clone T24/31.7), LY76/Ter119, LY6G (clone RB68C5) and PTPRC/CD45R (clone RA36B2), followed by incubation with anti-rat immunoglobulin-coupled magnetic beads (Qiagen Biomags, 310107).…”

Section: Discussionmentioning

confidence: 99%

Differential use of autophagy by primary dendritic cells specialized in cross-presentation

et al. 2015

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Abbreviations: 3-MA, 3-methyladenine; Atg7-DC CKO, Atg7 DC conditional knockout; BafA, bafilomycin A 1 ; CD, cluster of differentiation; CTL, cytotoxic T lymphocyte; DC, dendritic cell; DALIS, dendritic cell aggresome-like inducible structures; green fluorescent protein, GFP; IFC imaging flow cytometry; LAP, LC3 associated phagocytosis; LC3B, microtubule-associated protein 1 light chain 3 b; MHC II, major histocompatibility complex class II; MHC I, major histocompatibility complex class I; OVA, ovalbumin; OT-I, OVA-specific CD8 C T cell; OT-II, OVA-specific CD4 C T cell; SIM, structured illumination microscopy.Antigen-presenting cells survey their environment and present captured antigens bound to major histocompatibility complex (MHC) molecules. Formation of MHC-antigen complexes occurs in specialized compartments where multiple protein trafficking routes, still incompletely understood, converge. Autophagy is a route that enables the presentation of cytosolic antigen by MHC class II molecules. Some reports also implicate autophagy in the presentation of extracellular, endocytosed antigen by MHC class I molecules, a pathway termed "cross-presentation." The role of autophagy in cross-presentation is controversial. This may be due to studies using different types of antigen presenting cells for which the use of autophagy is not well defined. Here we report that active use of autophagy is evident only in DC subtypes specialized in cross-presentation. However, the contribution of autophagy to cross-presentation varied depending on the form of antigen: it was negligible in the case of cell-associated antigen or antigen delivered via receptor-mediated endocytosis, but more prominent when the antigen was a soluble protein. These findings highlight the differential use of autophagy and its machinery by primary cells equipped with specific immune function, and prompt careful reassessment of the participation of this endocytic pathway in antigen cross-presentation.

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Section: Discussionmentioning

confidence: 99%

Differential use of autophagy by primary dendritic cells specialized in cross-presentation

et al. 2015

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“…HBV, HBV subviral particles and HBV antigens are processed and presented by mouse monocytes and DCs. [44][45][46] Shimizu et al 47 demonstrated that primary splenic DCs from HBV-transgenic mice could present in vivo captured antigen to T cells. This information is most important in the context of immunomodulatory therapy for chronic HBV.…”

Section: Areas Of Further Investigationmentioning

confidence: 99%

Dissecting the dendritic cell controversy in chronic hepatitis B virus infection

Gehring

D’Angelo

2014

Cell Mol Immunol

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Therapeutic vaccines to boost endogenous T-cell immunity rely on the stimulatory capacity of dendritic cells (DCs). The functionality of DCs in chronic hepatitis B virus (HBV) infection has been a long-standing debate. Therefore, we have attempted to summarize multiple studies investigating DC function in chronic HBV patients to determine whether common observations can be drawn. We found that the frequency and function of ex vivo-tested myeloid and plasmacytoid DCs were largely intact in patients with HBV infection and similar to those of healthy donor DCs. The main exception was reduced IFN-a production by plasmacytoid DC from chronic HBV patients. This reduced IFN-a production correlated with liver inflammation in multiple studies but not with viral load, suggesting that viral antigens have little effect on DC function. The majority of the confusion about DC function arises from studies reporting the reduced function of healthy donor DCs exposed to various sources of HBV in vitro. These direct effects of viral antigens are in contrast to data from HBV-infected patients. The variations in the assays used and areas that require further investigation are also covered

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“…The use of biochemically modified HBsAgS VLPs, which induce enhanced immune responses may represent an alternative way to restore potent responses. The HBsAgS VLPs are processed by DCs and antigens presented via the major histocompatibility complex (MHC) class I and II antigen presentation pathways (10). In addition to HBsAgS VLPs being an immunogen of medical interest to prevent or to overcome HBV infections, the particles have been used as platforms for the delivery of foreign antigenic sequences and facilitated the induction of anti-foreign antigen-specific immune responses (11)(12)(13)(14)(15)(16)(17)(18).…”

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confidence: 99%

Modification of Asparagine-Linked Glycan Density for the Design of Hepatitis B Virus Virus-Like Particles with Enhanced Immunogenicity

Hyakumura

Walsh

Thaysen‐Andersen

et al. 2015

J Virol

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The small envelope proteins (HBsAgS) derived from hepatitis B virus (HBV) represent the antigenic components of the HBV vaccine and are platforms for the delivery of foreign antigenic sequences. To investigate structure-immunogenicity relationships for the design of improved immunization vectors, we have generated biochemically modified virus-like particles (VLPs) exhibiting glycoengineered HBsAgS. For the generation of hypoglycosylated VLPs, the wild-type (WT) HBsAgS N146 glycosylation site was converted to N146Q; for constructing hyperglycosylated VLPs, potential glycosylation sites were introduced in the HBsAgS external loop region at positions T116 and G130 in addition to the WT site. The introduced T116N and G130N sites were utilized as glycosylation anchors resulting in the formation of hyperglycosylated VLPs. Mass spectroscopic analyses showed that the hy-

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Hepatitis B virus-like particles access major histocompatibility class I and II antigen presentation pathways in primary dendritic cells

Cited by 23 publications

References 41 publications

Differential use of autophagy by primary dendritic cells specialized in cross-presentation

Differential use of autophagy by primary dendritic cells specialized in cross-presentation

Dissecting the dendritic cell controversy in chronic hepatitis B virus infection

Modification of Asparagine-Linked Glycan Density for the Design of Hepatitis B Virus Virus-Like Particles with Enhanced Immunogenicity

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