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Nature Reviews. Immunology Apr 2015Antigenic peptide-loaded MHC class II molecules (peptide-MHC class II) are constitutively expressed on the surface of professional antigen-presenting cells (APCs),... (Review)
Review
Antigenic peptide-loaded MHC class II molecules (peptide-MHC class II) are constitutively expressed on the surface of professional antigen-presenting cells (APCs), including dendritic cells, B cells, macrophages and thymic epithelial cells, and are presented to antigen-specific CD4(+) T cells. The mechanisms of antigen uptake, the nature of the antigen processing compartments and the lifetime of cell surface peptide-MHC class II complexes can vary depending on the type of APC. It is likely that these differences are important for the function of each distinct APC subset in the generation of effective adaptive immune responses. In this Review, we describe our current knowledge of the mechanisms of uptake and processing of antigens, the intracellular formation of peptide-MHC class II complexes, the intracellular trafficking of peptide-MHC class II complexes to the APC plasma membrane and their ultimate degradation.
Topics: Animals; Antigen Presentation; Antigen-Presenting Cells; Antigens; Cell Membrane; Epitopes; Histocompatibility Antigens Class II; Humans; Peptides; Protein Transport
PubMed: 25720354
DOI: 10.1038/nri3818 -
Molecular Therapy : the Journal of the... Dec 2022The full potential of tumor-infiltrating lymphocyte (TIL) therapy has been hampered by the inadequate activation and low persistence of TILs, as well as inefficient...
The full potential of tumor-infiltrating lymphocyte (TIL) therapy has been hampered by the inadequate activation and low persistence of TILs, as well as inefficient neoantigen presentation by tumors. We transformed tumor cells into artificial antigen-presenting cells (aAPCs) by infecting them with a herpes simplex virus 1 (HSV-1)-based oncolytic virus encoding OX40L and IL12 (OV-OX40L/IL12) to provide local signals for optimum T cell activation. The infected tumor cells displayed increased expression of antigen-presenting cell-related markers and induced enhanced T cell activation and killing in coculture with TILs. Combining OV-OX40L/IL12 and TIL therapy induced complete tumor regression in patient-derived xenograft and syngeneic mouse tumor models and elicited an antitumor immunological memory. In addition, the combination therapy produced aAPC properties in tumor cells, activated T cells, and reprogrammed macrophages to a more M1-like phenotype in the tumor microenvironment. This combination strategy unleashes the full potential of TIL therapy and warrants further evaluation in clinical studies.
Topics: Humans; Animals; Mice; Oncolytic Viruses; Lymphocytes, Tumor-Infiltrating; Antigen-Presenting Cells
PubMed: 35715953
DOI: 10.1016/j.ymthe.2022.06.010 -
International Journal of Molecular... Aug 2023Thrombocytes are numerous in the blood of aves (birds) and ichthyoids (fish). The origin of this cell type is a common hematopoietic stem cell giving rise to a cell that... (Review)
Review
Thrombocytes are numerous in the blood of aves (birds) and ichthyoids (fish). The origin of this cell type is a common hematopoietic stem cell giving rise to a cell that is active in blood coagulation, inflammatory functions, and the immune response in general. It has been well documented that thrombocytes can phagocytize small particles and bacteria. While phagocytosis with an associated oxidative burst has been reported for chicken thrombocytes, some questions remain as to the degradation capacity of phagosomes in ichthyoids. As innate cells, thrombocytes can be stimulated by bacterial, viral, and fungal pathogens to express altered gene expression. Furthermore, there have been observations that led researchers to state that platelets/thrombocytes are capable of serving as "professional antigen presenting cells" expressing CD40, CD80/86, MHC I, and MHC II. This indeed may be the case or, more likely at this time, provide supporting evidence that these cells aid and assist in the role of professional antigen-presenting cells to initiate adaptive immune responses.
Topics: Animals; Blood Platelets; Blood Coagulation; Antigen-Presenting Cells; B7-1 Antigen; Bacteriophages
PubMed: 37629130
DOI: 10.3390/ijms241612950 -
Journal of Immunology Research 2015In therapeutic antitumor vaccination, dendritic cells play the leading role since they decide if, how, when, and where a potent antitumor immune response will take... (Review)
Review
In therapeutic antitumor vaccination, dendritic cells play the leading role since they decide if, how, when, and where a potent antitumor immune response will take place. Since the disentanglement of the complexity and merit of different antigen-presenting cell subtypes, antitumor immunotherapeutic research started to investigate the potential benefit of targeting these subtypes in situ. This review will discuss which antigen-presenting cell subtypes are at play and how they have been targeted and finally question the true meaning of targeting antitumor-based vaccines.
Topics: Animals; Antigen-Presenting Cells; Antigens, Neoplasm; Cancer Vaccines; Dendritic Cells; Humans; Immunotherapy; Neoplasms
PubMed: 26583156
DOI: 10.1155/2015/785634 -
ACS Nano Sep 2022Nanosized artificial antigen-presenting cells (aAPCs), synthetic immune cell mimics that aim to activate T cells or , offer an effective alternative to cellular...
Nanosized artificial antigen-presenting cells (aAPCs), synthetic immune cell mimics that aim to activate T cells or , offer an effective alternative to cellular immunotherapies. However, comprehensive studies that delineate the effect of nano-aAPC topology, including nanoparticle morphology and ligand density, are lacking. Here, we systematically studied the topological effects of polymersome-based aAPCs on T cell activation. We employed an aAPC library created from biodegradable poly(ethylene glycol)--poly(d,l-lactide) (PEG-PDLLA) polymersomes with spherical or tubular shape and variable sizes, which were functionalized with αCD3 and αCD28 antibodies at controlled densities. Our results indicate that high ligand density leads to enhancement in T cell activation, which can be further augmented by employing polymersomes with larger size. At low ligand density, the effect of both polymersome shape and size was more pronounced, showing that large elongated polymersomes better activate T cells compared to their spherical or smaller counterparts. This study demonstrates the capacity of polymersomes as aAPCs and highlights the role of topology for their rational design.
Topics: Antigen-Presenting Cells; Immunotherapy; Ligands; Lymphocyte Activation; Polyethylene Glycols
PubMed: 35969506
DOI: 10.1021/acsnano.2c06211 -
Seminars in Immunology Mar 2023Cross-priming was first recognized in the context of in vivo cytotoxic T lymphocyte (CTL) responses generated against minor histocompatibility antigens induced by... (Review)
Review
Cross-priming was first recognized in the context of in vivo cytotoxic T lymphocyte (CTL) responses generated against minor histocompatibility antigens induced by immunization with lymphoid cells. Even though the basis for T cell antigen recognition was still largely unclear at that time, these early studies recognized the implication that such minor histocompatibility antigens were derived from the immunizing cells and were obtained exogenously by the host's antigen presenting cells (APCs) that directly prime the CTL response. As antigen recognition by the T cell receptor became understood to involve peptides derived from antigens processed by the APCs and presented by major histocompatibility molecules, the "cross-priming" phenomenon was subsequently recast as "cross-presentation" and the scope considered for examining this process gradually broadened to include many different forms of antigens, including soluble proteins, and different types of APCs that may not be involved in in vivo CTL priming. Many studies of cross-presentation have relied on in vitro cell models that were recently found to differ from in vivo APCs in particular mechanistic details. A recent trend has focused on the APCs and pathways of cross-presentation used in vivo, especially the type 1 dendritic cells. Current efforts are also being directed towards validating the in vivo role of various putative pathways and gene candidates in cross-presentation garnered from various in vitro studies and to determine the relative contributions they make to CTL responses across various forms of antigens and immunologic settings. Thus, cross-presentation appears to be carried by different pathways in various types of cells for different forms under different physiologic settings, which remain to be evaluated in an in vivo physiologic setting.
Topics: Humans; Antigen-Presenting Cells; Cross-Priming; T-Lymphocytes, Cytotoxic; Antigens; Minor Histocompatibility Antigens; Biology; Dendritic Cells; Antigen Presentation; Histocompatibility Antigens Class I
PubMed: 36645993
DOI: 10.1016/j.smim.2023.101711 -
Journal of Hepatology Feb 2011The liver is an organ in which several major pathogens evade immune clearance and achieve chronicity. How do they do it? Recent research has documented multiple... (Review)
Review
The liver is an organ in which several major pathogens evade immune clearance and achieve chronicity. How do they do it? Recent research has documented multiple mechanisms by which immune responses in the liver are biased towards tolerance. In this review, the induction of local, intrahepatic tolerance is explored from the perspective of antigen presentation. Experiments support the role not only of liver dendritic cell subsets but also of diverse subsets of unconventional antigen-presenting cells in inducing immune suppression. The literature on this topic is controversial and sometimes contradictory, making it difficult to formulate a unified model of antigen handling and T cell priming in the liver. Here I offer a critical review of the state of the art in understanding antigen presentation in the liver.
Topics: Animals; Antigen-Presenting Cells; Cell Movement; Dendritic Cells; Endothelial Cells; Hepatic Stellate Cells; Hepatocytes; Humans; Leukocytes; Liver
PubMed: 21084131
DOI: 10.1016/j.jhep.2010.10.005 -
Frontiers in Immunology 2018Professional antigen-presenting cells (APCs) include dendritic cells, monocytes, and B cells. APCs internalize and process antigens, producing immunogenic peptides that... (Review)
Review
Professional antigen-presenting cells (APCs) include dendritic cells, monocytes, and B cells. APCs internalize and process antigens, producing immunogenic peptides that enable antigen presentation to T lymphocytes, which provide the signals that trigger T-cell activation, proliferation, and differentiation, and lead to adaptive immune responses. After detection of microbial antigens through pattern recognition receptors (PRRs), APCs migrate to secondary lymphoid organs where antigen presentation to T lymphocytes takes place. Tetraspanins are membrane proteins that organize specialized membrane platforms, called tetraspanin-enriched microdomains, which integrate membrane receptors, like PRR and major histocompatibility complex class II (MHC-II), adhesion proteins, and signaling molecules. Importantly, through the modulation of the function of their associated membrane partners, tetraspanins regulate different steps of the immune response. Several tetraspanins can positively or negatively regulate the activation threshold of immune receptors. They also play a role during migration of APCs by controlling the surface levels and spatial arrangement of adhesion molecules and their subsequent intracellular signaling. Finally, tetraspanins participate in antigen processing and are important for priming of naïve T cells through the control of T-cell co-stimulation and MHC-II-dependent antigen presentation. In this review, we discuss the role of tetraspanins in APC biology and their involvement in effective immune responses.
Topics: Animals; Antigen Presentation; Antigen-Presenting Cells; Cell Movement; Dendritic Cells; Histocompatibility Antigens Class II; Humans; Immunomodulation; Protein Transport; Receptors, Pattern Recognition; Tetraspanins
PubMed: 29875769
DOI: 10.3389/fimmu.2018.01074 -
Frontiers in Immunology 2023Sepsis is a life-threatening condition with high mortality. A few studies have emerged utilizing single-cell RNA sequencing (scRNA-seq) to analyze gene expression at the...
BACKGROUND
Sepsis is a life-threatening condition with high mortality. A few studies have emerged utilizing single-cell RNA sequencing (scRNA-seq) to analyze gene expression at the single-cell resolution in sepsis, but a comprehensive high-resolution analysis of blood antigen-presenting cells has not been conducted.
METHODS
All published human scRNA-seq data were downloaded from the single cell portal database. After manually curating the dataset, we extracted all antigen-presenting cells, including dendritic cells (DCs) and monocytes, for identification of cell subpopulations and their gene profiling and intercellular interactions between septic patients and healthy controls. Finally, we further validated the findings by performing deconvolution analysis on bulk RNA sequencing (RNA-seq) data and flow cytometry.
RESULTS
Within the traditional DC populations, we discovered novel anergic DC subtypes characterized by low major histocompatibility complex class II expression. Notably, these anergic DC subtypes showed a significant increase in septic patients. Additionally, we found that a previously reported immunosuppressive monocyte subtype, Mono1, exhibited a similar gene expression profile to these anergic DCs. The consistency of our findings was confirmed through validation using bulk RNA-seq and flow cytometry, ensuring accurate identification of cell subtypes and gene expression patterns.
CONCLUSIONS
This study represents the first comprehensive single-cell analysis of antigen-presenting cells in human sepsis, revealing novel disease-associated anergic DC subtypes. These findings provide new insights into the cellular mechanisms of immune dysregulation in bacterial sepsis.
Topics: Humans; Dendritic Cells; Clonal Anergy; Monocytes; Sepsis; Single-Cell Analysis
PubMed: 37781404
DOI: 10.3389/fimmu.2023.1257572 -
Current Opinion in Organ Transplantation Feb 2018To evaluate role of the lymph node in immune regulation and tolerance in transplantation and recent advances in the delivery of antigen and immune modulatory signals to... (Review)
Review
PURPOSE OF REVIEW
To evaluate role of the lymph node in immune regulation and tolerance in transplantation and recent advances in the delivery of antigen and immune modulatory signals to the lymph node.
RECENT FINDINGS
Lymph nodes are a primary site of immune cell priming, activation, and modulation, and changes within the lymph node microenvironment have the potential to induce specific regulation, suppression, and potentially tolerance. Antigen enters the lymph node either from tissues via lymphatics, from blood via high endothelial venules, or directly via injection. Here we review different techniques and materials to deliver antigen to the lymph node including microparticles or nanoparticles, ex-vivo antigen presenting cell manipulation, and use of receptor conjugation for specific intralymph node targeting locations.
SUMMARY
The promising results point to powerful techniques to harness the lymph node microenvironment and direct systemic immune regulation. The materials, techniques, and approaches suggest that translational and clinical trials in nonhuman primate and patients may soon be possible.
Topics: Animals; Antigen-Presenting Cells; Graft Rejection; Humans; Immune Tolerance; Immunologic Factors; Lymph Nodes; Nanomedicine
PubMed: 29189412
DOI: 10.1097/MOT.0000000000000488