The Experts below are selected from a list of 52500 Experts worldwide ranked by ideXlab platform
Alexander Y Rudensky - One of the best experts on this subject based on the ideXlab platform.
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the lysosomal cysteine proteases in mhc class ii Antigen Presentation
Immunological Reviews, 2005Co-Authors: Lianne C Hsing, Alexander Y RudenskyAbstract:Summary: The endosomal pathway of Antigen Presentation leads to the display of peptides on major histocompatibility complex (MHC) class II molecules at the cell surface of Antigen-presenting cells (APCs). The pathway involves two major steps, invariant chain degradation and Antigen processing, which take place in the late endosomes/lysosomes. So far, of the known lysosomal proteases, only cathepsin L and cathepsin S have been shown to have a non-redundant role in endosomal Presentation in vivo. Besides being engaged in the degradation of invariant chain, these enzymes also mediate the processing of Antigens in distinct cell types. Surprisingly, these enzymes are active in different types of APCs, and this defined expression pattern seems to be enforced by regulatory mechanisms acting on multiple levels.
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lysosomal cysteine proteases regulate Antigen Presentation
Nature Reviews Immunology, 2003Co-Authors: Karen Honey, Alexander Y RudenskyAbstract:Antigen Presentation by both classical MHC class II molecules and the non-classical MHC class I-like molecule CD1D requires their entry into the endosomal/lysosomal compartment. Lysosomal cysteine proteases constitute an important subset of the enzymes that are present in this compartment and, here, we discuss the role of these proteases in regulating Antigen Presentation by both MHC class II and CD1D molecules.
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Altered Antigen Presentation in Mice Lacking H2-O
Immunity, 1998Co-Authors: Monika Liljedahl, Luc Teyton, Anders Brunmark, Ola Winqvist, Per A Peterson, Phillip Wong, Charles D. Surh, Alexander Y Rudensky, Wai-ping Fung-leungAbstract:Abstract HLA-DM catalyzes the release of MHC class II–associated invariant chain–derived peptides (CLIP) from class II molecules. Recent evidence has suggested that HLA-DO is a negative regulator of HLA-DM in B cells, but the physiological function of HLA-DO remains unclear. Analysis of Antigen Presentation by B cells from mice lacking H2-O (the mouse equivalent of HLA-DO), together with biochemical analysis using purified HLA-DO and HLA-DM molecules, suggests that HLA-DO/H2-O influences the peptide loading of class II molecules by limiting the pH range in which HLA-DM is active. This effect may serve to decrease the Presentation of Antigens internalized by fluid-phase endocytosis, thus concentrating the B cell–mediated Antigen Presentation to Antigens internalized by membrane immunoglobulin.
Marlieke L M Jongsma - One of the best experts on this subject based on the ideXlab platform.
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pakc a novel panel of hla class i Antigen Presentation machinery knockout cells from the same genetic origin
European Journal of Immunology, 2021Co-Authors: Antonius A De Waard, Tamara Verkerk, Marlieke L M Jongsma, Kelly Hoefakker, Sunesh Sethumadhavan, Carolin Gerke, Sophie Bliss, Xiangrui Kong, George M C JanssenAbstract:A single model system for integrative studies on multiple facets of Antigen Presentation is lacking. PAKC is a novel panel of ten cell lines knocked out for individual components of the HLA class I Antigen Presentation pathway. PAKC will accelerate HLA-I research in the fields of oncology, infectiology, and autoimmunity.
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pakc a novel panel of hla class i Antigen Presentation machinery knockout cells from the same genetic origin
bioRxiv, 2020Co-Authors: Antonius A De Waard, Tamara Verkerk, Marlieke L M Jongsma, Kelly Hoefakker, Sunesh Sethumadhavan, Carolin Gerke, Sophie Bliss, George M C Janssen, Frans H J Claas, Arend MulderAbstract:Abstract With the emergence of immunotherapies, the understanding of functional HLA class I Antigen Presentation to T cells is more relevant than ever. Current knowledge on Antigen Presentation is based on decades of research in a wide variety of cell types with varying Antigen Presentation machinery (APM) expression patterns, proteomes and HLA haplotypes. This diversity complicates the establishment of individual APM contributions to Antigen generation, selection and Presentation. Therefore, we generated a novel Panel of APM Knockout Cell lines (PAKC) from the same genetic origin. After CRISPR/Cas9 genome-editing of ten individual APM components in a human cell line, we derived clonal cell lines and confirmed their knockout status and phenotype. We then show how PAKC will accelerate research on the functional interplay between APM components and their role in Antigen generation and Presentation. This will lead to improved understanding of peptide-specific T cell responses in infection, cancer and autoimmunity. Key points We generated a panel of cell lines to study HLA class I Antigen Presentation We show how this will spark research in infection, tumor biology and autoimmunity
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towards a systems understanding of mhc class i and mhc class ii Antigen Presentation
Nature Reviews Immunology, 2011Co-Authors: Jacques Neefjes, Marlieke L M Jongsma, Petra Paul, Oddmund BakkeAbstract:The molecular details of Antigen processing and Presentation by MHC class I and class II molecules have been studied extensively for almost three decades. Although the basic principles of these processes were laid out approximately 10 years ago, the recent years have revealed many details and provided new insights into their control and specificity. MHC molecules use various biochemical reactions to achieve successful Presentation of Antigenic fragments to the immune system. Here we present a timely evaluation of the biology of Antigen Presentation and a survey of issues that are considered unresolved. The continuing flow of new details into our understanding of the biology of MHC class I and class II Antigen Presentation builds a system involving several cell biological processes, which is discussed in this Review.
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a genome wide multidimensional rnai screen reveals pathways controlling mhc class ii Antigen Presentation
Cell, 2011Co-Authors: Petra Paul, Marlieke L M Jongsma, Peter Cresswell, Tineke Van Den Hoorn, Mark J Bakker, Rutger Hengeveld, Lennert Janssen, David A Egan, Marieke Van Ham, Anja Ten BrinkeAbstract:MHC class II molecules (MHC-II) present peptides to T helper cells to facilitate immune responses and are strongly linked to autoimmune diseases. To unravel processes controlling MHC-II Antigen Presentation, we performed a genome-wide flow cytometry-based RNAi screen detecting MHC-II expression and peptide loading followed by additional high-throughput assays. All data sets were integrated to answer two fundamental questions: what regulates tissue-specific MHC-II transcription, and what controls MHC-II transport in dendritic cells? MHC-II transcription was controlled by nine regulators acting in feedback networks with higher-order control by signaling pathways, including TGFβ. MHC-II transport was controlled by the GTPase ARL14/ARF7, which recruits the motor myosin 1E via an effector protein ARF7EP. This complex controls movement of MHC-II vesicles along the actin cytoskeleton in human dendritic cells (DCs). These genome-wide systems analyses have thus identified factors and pathways controlling MHC-II transcription and transport, defining targets for manipulation of MHC-II Antigen Presentation in infection and autoimmunity.
Jose A. Villadangos - One of the best experts on this subject based on the ideXlab platform.
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Antigen-Presentation Properties of Plasmacytoid Dendritic Cells
Immunity, 2008Co-Authors: Jose A. Villadangos, Louise YoungAbstract:One of the remaining enigmas of the dendritic cell (DC) network is the potential contribution of plasmacytoid DCs (pDCs) to Antigen Presentation. Although the Antigen-Presentation capacity of conventional DCs (cDCs) is clearly defined, pDCs are generally attributed as having little, if any, Antigen-Presentation function. Instead, pDCs are regarded as immunomodulating cells, capable of directing the immune response through their secretion of large amounts of type I interferons. In this review, we examine the evidence for a potential role of pDC in Antigen capture, processing, and Presentation to T cells at sites of infection and in the lymph nodes.
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cathepsins b and d are dispensable for major histocompatibility complex class ii mediated Antigen Presentation
Proceedings of the National Academy of Sciences of the United States of America, 1998Co-Authors: Jan M Deussing, Hidde L Ploegh, Wera Roth, Paul Saftig, Christoph Peters, Jose A. VilladangosAbstract:Antigen Presentation by major histocompatibility complex (MHC) class II molecules requires the participation of different proteases in the endocytic route to degrade endocytosed Antigens as well as the MHC class II-associated invariant chain (Ii). Thus far, only the cysteine protease cathepsin (Cat) S appears essential for complete destruction of Ii. The enzymes involved in degradation of the Antigens themselves remain to be identified. Degradation of Antigens in vitro and experiments using protease inhibitors have suggested that Cat B and Cat D, two major aspartyl and cysteine proteases, respectively, are involved in Antigen degradation. We have analyzed the Antigen-presenting properties of cells derived from mice deficient in either Cat B or Cat D. Although the absence of these proteases provoked a modest shift in the efficiency of Presentation of some Antigenic determinants, the overall capacity of Cat B-/- or Cat D-/- Antigen-presenting cells was unaffected. Degradation of Ii proceeded normally in Cat B-/- splenocytes, as it did in Cat D-/- cells. We conclude that neither Cat B nor Cat D are essential for MHC class II-mediated Antigen Presentation.
Jacques Neefjes - One of the best experts on this subject based on the ideXlab platform.
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towards a systems understanding of mhc class i and mhc class ii Antigen Presentation
Nature Reviews Immunology, 2011Co-Authors: Jacques Neefjes, Marlieke L M Jongsma, Petra Paul, Oddmund BakkeAbstract:The molecular details of Antigen processing and Presentation by MHC class I and class II molecules have been studied extensively for almost three decades. Although the basic principles of these processes were laid out approximately 10 years ago, the recent years have revealed many details and provided new insights into their control and specificity. MHC molecules use various biochemical reactions to achieve successful Presentation of Antigenic fragments to the immune system. Here we present a timely evaluation of the biology of Antigen Presentation and a survey of issues that are considered unresolved. The continuing flow of new details into our understanding of the biology of MHC class I and class II Antigen Presentation builds a system involving several cell biological processes, which is discussed in this Review.
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making sense of mass destruction quantitating mhc class i Antigen Presentation
Nature Reviews Immunology, 2003Co-Authors: Jonathan W Yewdell, Eric Reits, Jacques NeefjesAbstract:MHC class I molecules bind short peptides and present them to CD8+ T cells. Contrary to textbook descriptions, the generation of MHC class-I-associated peptides from endogenous proteins is a highly dynamic and remarkably inefficient process. Here, we describe recent experiments that show how nascent and mature proteins are degraded into peptides that are trimmed, transported and trimmed again to enable Presentation of a small portion of the generated peptides. By linking the failure rate of protein synthesis with Antigen Presentation, a rapid T-cell response is ensured, which is crucial in combating viral infections. Presentation on MHC class I molecules is achieved by less than 0.1% of the specific peptides that have survived intracellular destruction. The other peptides are converted into free amino acids that are used for recycling into new proteins.
Sebastian Amigorena - One of the best experts on this subject based on the ideXlab platform.
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reactive oxygen species production in the phagosome impact on Antigen Presentation in dendritic cells
Antioxidants & Redox Signaling, 2013Co-Authors: Fiorella Kotsias, Sebastian Amigorena, Eik Hoffmann, Ariel SavinaAbstract:Abstract Significance: The NADPH oxidase 2 (NOX2) is known to play a major role in innate immunity for several decades. Phagocytic cells provide host defense by ingesting microbes and destroy them by different mechanisms, including the generation of reactive oxygen species (ROS) by NOX2, a process known as oxidative burst. The phagocytic pathway of dendritic cells (DCs), highly adapted to Antigen processing, has been shown to display remarkable differences compared to other phagocytes. Contrary to macrophages and neutrophils, the main function of DC phagosomes is Antigen Presentation rather than pathogen killing or clearance of cell debris. Recent Advances: In the last few years, it became clear that NOX2 is also involved in the establishment of adaptive immunity. Several studies support the idea of a relationship between Antigen Presentation and the level of Antigen degradation, the latter one being regulated by the pH and ROS within phagosomes. Critical Issues: The regulation of phagosomal pH exerted by...
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phagocytosis and Antigen Presentation in dendritic cells
Immunological Reviews, 2007Co-Authors: Ariel Savina, Sebastian AmigorenaAbstract:Like macrophages and neutrophils, dendritic cells (DCs) are considered professional phagocytes. Even if the three cell types phagocytose parasites, bacteria, cell debris, or even intact cells very efficiently, the functional outcomes of the phagocytic event are quite different. Macrophages and neutrophils scavenge and destroy phagocytosed particles, a critical step in innate immunity. DCs, in contrast, have developed means to 'preserve' useful information from the ingested particles that serve to initiate adaptive immune responses. Thus, both phagosomal degradation and acidification are much lower in DCs than in macrophages or neutrophils. Reduced degradation results in the conservation of Antigenic peptides and in their increased Presentation on major histocompatibility complex class I and II molecules. In this article, we review the mechanisms that control this delicate equilibrium between phagosomal degradation/cytotoxicity and Antigen Presentation in the different families of phagocytes.
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Antigen Presentation and t cell stimulation by dendritic cells
Annual Review of Immunology, 2002Co-Authors: Pierre Guermonprez, Jenny Valladeau, Laurence Zitvogel, Clotilde Thery, Sebastian AmigorenaAbstract:Dendritic cells take up Antigens in peripheral tissues, process them into proteolytic peptides, and load these peptides onto major histocompatibility complex (MHC) class I and II molecules. Dendritic cells then migrate to secondary lymphoid organs and become competent to present Antigens to T lymphocytes, thus initiating Antigen-specific immune responses, or immunological tolerance. Antigen Presentation in dendritic cells is finely regulated: Antigen uptake, intracellular transport and degradation, and the traffic of MHC molecules are different in dendritic cells as compared to other Antigen-presenting cells. These specializations account for dendritic cells' unique role in the initiation of immune responses and the induction of tolerance.