Faculty Opinions recommendation of TLR signals induce phagosomal MHC-I delivery from the endosomal recycling compartment to allow cross-presentation.

Abstract Background: Biomimetic nanoparticles have potential applications in many fields for their favorable properties. Results: Here, we developed a self-adjuvanting biomimetic anti-tumor nanovaccine, which was self-assembled with an amphiphilic conjugate synthetized with phospholipids of 1, 2-Dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and hydrophilic Toll-like receptor (TLR9) agonists CpG ODN. The nanovaccine could not only provide effective initial antigens stimulation and sustained long-term antigen supply with a controlled release, but also induce antigens cross-presentation via MHC-I pathway initiating CD8+ T-cell responses. Moreover, the dense nucleotides shell around the nanovaccine could promote antigens endocytosis via various receptor-mediated pathways into dendritic cells. And CpG ODN interacted with TLR9 triggering the cytokines secretion of TNF-α and IL-10 further boosted the anti-tumor humoral and cellular immune responses, which led to significant tumor suppressive effect and remarkable survival prolongation. Conclusions: So, this nanovaccine self-assembled with phospholipid-nucleotide amphiphiles can serve as a safe, simple and efficient approach for anti-tumor immunotherapy.

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Myeloid and Plasmacytoid Dendritic Cells and Cancer – New Insights

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2019.735 ◽

2019 ◽

Vol 7 (19) ◽

pp. 3324-3340 ◽

Cited By ~ 1

Author(s):

Maya Gulubova ◽

Koni Vancho Ivanova ◽

Mehmed Hadzhi ◽

Dimitur Chonov ◽

Maria Magdalena Ignatova ◽

...

Keyword(s):

Dendritic Cells ◽

Immune Responses ◽

Cell Types ◽

Tumour Microenvironment ◽

Mhc I ◽

Cross Presentation ◽

Adaptive Immune ◽

Histocompatibility Complex ◽

T Helpers

Dendritic cells (DCs) use effective mechanisms to combat antigens and to bring about adaptive immune responses through their ability to stimulate nӓive T cells. At present, four major cell types are categorised as DCs: Classical or conventional (cDCs), Plasmacytoid (pDCs), Langerhans cells (LCs), and monocyte-derived DCs (Mo-DCs). It was suggested that pDCs, CD1c+ DCs and CD141+ DCs in humans are equivalent to mouse pDCs, CD11b+ DCs and CD8α+ DCs, respectively. Human CD141+ DCs compared to mouse CD8α+ DCs have remarkable functional and transcriptomic similarities. Characteristic markers, transcription factors, toll-like receptors, T helpers (Th) polarisation, cytokines, etc. of DCs are discussed in this review. Major histocompatibility complex (MHC) I and II antigen presentation, cross-presentation and Th polarisation are defined, and the dual role of DCs in the tumour is discussed. Human DCs are the main immune cells that orchestrate the immune response in the tumour microenvironment.

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A cell-penetrating peptide-assisted nanovaccine promotes antigen cross-presentation and anti-tumor immune response

Biomaterials Science ◽

10.1039/c9bm01183h ◽

2019 ◽

Vol 7 (12) ◽

pp. 5516-5527 ◽

Cited By ~ 4

Author(s):

Xiaoxuan Liu ◽

Jiale Liu ◽

Dan Liu ◽

Yanfeng Han ◽

Haiyan Xu ◽

...

Keyword(s):

Immune Response ◽

Major Histocompatibility Complex ◽

Cell Penetrating Peptide ◽

Complex Class ◽

Class I Mhc ◽

Mhc I ◽

Cross Presentation ◽

Histocompatibility Complex ◽

Cell Penetrating ◽

A Cell

Exogenous antigens processed in the cytosol and subsequently cross-presented on major histocompatibility complex class I (MHC-I) molecules activate cytotoxic CD8+ lymphocytes (CTL), which are crucial in cancer immunotherapy.

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Preclinical Studies of a Modified Vaccinia Virus Ankara-Based HIV Candidate Vaccine: Antigen Presentation and Antiviral Effect

Journal of Virology ◽

10.1128/jvi.02329-09 ◽

2010 ◽

Vol 84 (10) ◽

pp. 5314-5328 ◽

Cited By ~ 31

Author(s):

Samantha Brandler ◽

Alice Lepelley ◽

Marion Desdouits ◽

Florence Guivel-Benhassine ◽

Pierre-Emmanuel Ceccaldi ◽

...

Keyword(s):

Vaccinia Virus ◽

Antiviral Effect ◽

Vaccine Antigen ◽

Type I ◽

Hiv Replication ◽

National Agency ◽

Class I Mhc ◽

Mhc I ◽

Cross Presentation ◽

Modified Vaccinia Virus Ankara

ABSTRACT Poxvirus-based human immunodeficiency virus (HIV) vaccine candidates are currently under evaluation in preclinical and clinical trials. Modified vaccinia virus Ankara (MVA) vectors have excellent safety and immunogenicity records, but their behavior in human cell cultures remains only partly characterized. We studied here various virological and immunological aspects of the interactions of MVA-HIV, a vaccine candidate developed by the French National Agency for AIDS Research (ANRS), with primary human cells. We report that MVA-HIV infects and drives Gag expression in primary macrophages, dendritic cells (DCs), and epithelial and muscle cells. MVA-HIV-infected DCs matured, efficiently presented Gag, Pol, and Nef antigens, and activated HIV-specific cytotoxic T lymphocytes (CTLs). As expected with this type of vector, infection was cytopathic and led to DC apoptosis. Coculture of MVA-HIV-infected epithelial cells or myotubes with DCs promoted efficient Gag antigen major histocompatibility complex class I (MHC-I) cross-presentation without inducing direct infection and death of DCs. Antigen-presenting cells (APCs) infected with MVA-HIV also activated HIV-specific CD4+ T cells. Moreover, exposure of DCs to MVA-HIV or to MVA-HIV-infected myotubes induced type I interferon (IFN) production and inhibited subsequent HIV replication and transfer to lymphocytes. Altogether, these results show that MVA-HIV promotes efficient MHC-I and MHC-II presentation of HIV antigens by APCs without facilitating HIV replication. Deciphering the immune responses to MVA in culture experiments will help in the design of innovative vaccine strategies.

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HLA-F and MHC-I Open Conformers Cooperate in a MHC-I Antigen Cross-Presentation Pathway

The Journal of Immunology ◽

10.4049/jimmunol.1300080 ◽

2013 ◽

Vol 191 (4) ◽

pp. 1567-1577 ◽

Cited By ~ 36

Author(s):

Jodie P. Goodridge ◽

Ni Lee ◽

Aura Burian ◽

Chul-Woo Pyo ◽

Scott S. Tykodi ◽

...

Keyword(s):

Mhc I ◽

Cross Presentation ◽

Presentation Pathway

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Genomic programming of antigen cross-presentation in IRF4-expressing human Langerhans cells

10.1101/541383 ◽

2019 ◽

Cited By ~ 1

Author(s):

Marta E Polak ◽

Sofia Sirvent ◽

Kalum Clayton ◽

James Davies ◽

Andres F. Vallejo ◽

...

Keyword(s):

Dendritic Cells ◽

Transcription Factor ◽

Antigen Presentation ◽

Langerhans Cells ◽

Mhc I ◽

Cross Presentation ◽

Mhc Ii ◽

T Cell Immune Responses ◽

Dependent Protein ◽

Chromatin Profiling

AbstractLangerhans cells (LCs) in the epidermis present MHC I and MHC II-restricted antigens thereby priming either CD8 or CD4 T cell immune responses. The genomic programs and transcription factors regulating antigen presentation in LCs remain to be elucidated. We show human LCs are highly efficient in MHC I-antigen cross-presentation but lack the transcription factor IRF8 that is critical in dendritic cells. LC migration from the epidermis enhances their ability to cross-present antigens and is accompanied by the induction of the transcription factor IRF4, whose expression is correlated by scRNA-seq with genes involved in ubiquitin-dependent protein degradation. Chromatin profiling reveals enrichment of EICE and AICE composite DNA binding motifs in regulatory regions of antigen-presentation genes, which can be recognized by IRF4 in conjunction with PU.1 or BATF3 expressed in LCs. Thus, the genomic programming of human LCs including inducible expression of IRF4 with enhanced cross-presentation distinguishes them from conventional dendritic cells.

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Platelet EVs contain an active proteasome involved in protein processing for antigen presentation via MHC-I molecules

Blood ◽

10.1182/blood.2020009957 ◽

2021 ◽

Author(s):

Genevieve Marcoux ◽

Audrée Laroche ◽

Stephan Hasse ◽

Marie Bellio ◽

Maroua Mbarik ◽

...

Keyword(s):

Antigen Presentation ◽

Protein Processing ◽

Functional Protein ◽

Mhc I ◽

Cross Presentation ◽

System A ◽

Activated Platelets ◽

T Lymphocyte Proliferation ◽

Cd8 T Lymphocyte ◽

Spleen And Lymph Nodes

In addition to their hemostatic role, platelets play a significant role in immunity. Once activated, platelets release extracellular vesicles (EVs) formed by budding of their cytoplasmic membranes. Because of their heterogeneity, platelet EVs (PEVs) are thought to perform diverse functions. It is unknown, however, whether the proteasome is transferred from platelets to PEVs or whether its function is retained. We hypothesized that functional protein processing and antigen presentation machinery is transferred to PEVs by activated platelets. Using molecular and functional assays, we show that the active 20S proteasome is enriched in PEVs along with MHC-I and lymphocyte costimulatory molecules (CD40L and OX40L). Proteasome-containing PEVs were identified in healthy donor blood, but did not increase in platelet concentrates that caused adverse transfusion reactions. They were, however, augmented after immune complex injections in mice. The complete biodistribution of murine PEVs following injection into mice revealed that they could principally reach lymphoid organs such as spleen and lymph nodes, in addition to the bone marrow, and to a lesser extent liver and lungs. The PEV proteasome processed exogenous ovalbumin (OVA) and loaded its antigenic peptide onto MHC-I molecules which promoted OVA-specific CD8+ T lymphocyte proliferation. These results suggest that PEVs contribute to adaptive immunity through cross-presentation of antigens and have privileged access to immune cells through the lymphatic system, a tissue location that is inaccessible to platelets.

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