scholarly journals Pseudorabies virus US3- and UL49.5-dependent and -independent downregulation of MHC I cell surface expression in different cell types

Virology ◽  
2009 ◽  
Vol 395 (2) ◽  
pp. 172-181 ◽  
Author(s):  
Matthias J. Deruelle ◽  
Céline Van den Broeke ◽  
Hans J. Nauwynck ◽  
Thomas C. Mettenleiter ◽  
Herman W. Favoreel
Keyword(s):  
Cell Surface ◽  
Pseudorabies Virus ◽  
Cell Types ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Mhc I ◽  
Different Cell Types

scholarly journals Phosphorylation and internalization of gp130 occur after IL-6 activation of Jak2 kinase in hepatocytes.

1994 ◽  
Vol 5 (7) ◽  
pp. 819-828 ◽  
Author(s):  
Y Wang ◽  
G M Fuller
Keyword(s):  
Protein Synthesis ◽  
Cell Surface ◽  
De Novo ◽  
Cell Types ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Protein Synthesis Inhibitors ◽  
Different Cell Types ◽  
Kinetics Of

Recent evidence has shown that members of the Jak kinase family are activated after IL-6 binds to its receptor complex, leading to a tyrosine phosphorylation of gp130, the IL-6 signal-transducing subunit. The different members of the IL-6 cytokine subfamily induce distinct patterns of Jak-Tyk phosphorylation in different cell types. Using monospecific antibodies to gp130, Jak2 kinase, and phosphotyrosine, we investigated the kinetics of IL-6 stimulation of members of this pathway in primary hepatocytes. Our findings show that Jak 2 is maximally activated within 2 min of exposure to IL-6, followed by gp130 phosphorylation that reaches its peak in another 2 min then declines to basal level by 60 min. In vitro phosphorylation experiments show that activated Jak 2 is able to phosphorylate both native gp130 and a fusion peptide containing its cytoplasmic domain, demonstrating gp130 is a direct substrate of Jak 2 kinase. Experiments designed to explore the cell surface expression of gp130 show that > or = 2 h are required to get a second round of phosphorylation after the addition of more cytokines. This finding suggests that activated gp130 is internalized from the cell surface after IL-6 stimulation. Additional experiments using protein synthesis inhibitors reveal that new protein synthesis is required to get a second cycle of gp130 phosphorylation indicating gp130 must be synthesized de novo and inserted into the membrane. These findings provide strong evidence that down regulation of the IL-6 signal in hepatocytes involves the internalization and cytosol degradation of gp130.

scholarly journals Comparative Mutagenesis of Pseudorabies Virus and Epstein-Barr Virus gH Identifies a Structural Determinant within Domain III of gH Required for Surface Expression and Entry Function

2015 ◽  
Vol 90 (5) ◽  
pp. 2285-2293 ◽  
Author(s):  
Britta S. Möhl ◽  
Christina Schröter ◽  
Barbara G. Klupp ◽  
Walter Fuchs ◽  
Thomas C. Mettenleiter ◽  
...  
Keyword(s):  
Amino Acids ◽  
Cell Surface ◽  
B Cell ◽  
Epstein Barr Virus ◽  
Pseudorabies Virus ◽  
Surface Expression ◽  
Structural Motif ◽  
Cell Surface Expression ◽  
Barr Virus ◽  
Epstein Barr

ABSTRACTHerpesviruses infect cells using the conserved core fusion machinery composed of glycoprotein B (gB) and gH/gL. The gH/gL complex plays an essential but still poorly characterized role in membrane fusion and cell tropism. Our previous studies demonstrated that the conserved disulfide bond (DB) C278/C335 in domain II (D-II) of Epstein-Barr virus (EBV) gH has an epithelial cell-specific function, whereas the interface of D-II/D-III is involved in formation of the B cell entry complex by binding to gp42. To extend these studies, we compared gH of the alphaherpesvirus pseudorabies virus (PrV) with gH of the gammaherpesvirus EBV to identify functionally equivalent regions critical for gH function during entry. We identified several conserved amino acids surrounding the conserved DB that connects three central helices of D-III of PrV and EBV gH. The present study verified that the conserved DB and several contacting amino acids in D-III modulate cell surface expression and thereby contribute to gH function. In line with this finding, we found that DB C404/C439 and T401 are important for cell-to-cell spread and efficient entry of PrV. This parallel comparison between PrV and EBV gH function brings new insights into how gH structure impacts fusion function during herpesvirus entry.IMPORTANCEThe alphaherpesvirus PrV is known for its neuroinvasion, whereas the gammaherpesvirus EBV is associated with cancer of epithelial and B cell origin. Despite low amino acid conservation, PrV gH and EBV gH show strikingly similar structures. Interestingly, both PrV gH and EBV gH contain a structural motif composed of a DB and supporting amino acids which is highly conserved within theHerpesviridae. Our study verified that PrV gH uses a minimal motif with the DB as the core, whereas the DB of EBV gH forms extensive connections through hydrogen bonds to surrounding amino acids, ensuring the cell surface expression of gH/gL. Our study verifies that the comparative analysis of distantly related herpesviruses, such as PrV and EBV, allows the identification of common gH functions. In addition, we provide an understanding of how functional domains can evolve over time, resulting in subtle differences in domain structure and function.

scholarly journals Variations in MHC class I antigen presentation and immunopeptidome selection pathways

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1177
Author(s):  
Anita J. Zaitouna ◽  
Amanpreet Kaur ◽  
Malini Raghavan
Keyword(s):  
Cell Surface ◽  
Antigen Presentation ◽  
Surface Expression ◽  
Structural Features ◽  
Class I ◽  
Cell Surface Expression ◽  
Immune Recognition ◽  
Antigen Receptors ◽  
Class I Mhc ◽  
Mhc I

Major histocompatibility class I (MHC-I) proteins mediate immunosurveillance against pathogens and cancers by presenting antigenic or mutated peptides to antigen receptors of CD8+ T cells and by engaging receptors of natural killer (NK) cells. In humans, MHC-I molecules are highly polymorphic. MHC-I variations permit the display of thousands of distinct peptides at the cell surface. Recent mass spectrometric studies have revealed unique and shared characteristics of the peptidomes of individual MHC-I variants. The cell surface expression of MHC-I–peptide complexes requires the functions of many intracellular assembly factors, including the transporter associated with antigen presentation (TAP), tapasin, calreticulin, ERp57, TAP-binding protein related (TAPBPR), endoplasmic reticulum aminopeptidases (ERAPs), and the proteasomes. Recent studies provide important insights into the structural features of these factors that govern MHC-I assembly as well as the mechanisms underlying peptide exchange. Conformational sensing of MHC-I molecules mediates the quality control of intracellular MHC-I assembly and contributes to immune recognition by CD8 at the cell surface. Recent studies also show that several MHC-I variants can follow unconventional assembly routes to the cell surface, conferring selective immune advantages that can be exploited for immunotherapy.

scholarly journals Both Freshly Prepared and Frozen-Stored Amniotic Membrane Cells Express the Complement Inhibitor CD59

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Ágnes Füst ◽  
Éva Pállinger ◽  
Adrienn Stündl ◽  
Eszter Kovács ◽  
László Imre ◽  
...  
Keyword(s):  
Cell Surface ◽  
Amniotic Membrane ◽  
Ocular Surface ◽  
Cell Types ◽  
Surface Expression ◽  
Mesenchymal Cells ◽  
Cell Surface Expression ◽  
Complement Inhibitor ◽  
Becton Dickinson ◽  
Intracellular Expression

Amniotic membrane proved to be very effective tool in the treatment of a number of ocular surface diseases. The amniotic membrane, however, has to be stored before its transplantation onto the ocular surface followed by mandatory serologic control in order to exclude the transmission of certain viruses. Therefore it is most important to study if cryopreservation of the membrane affects cell surface expression of the molecules. We measured cell surface expression of CD59, a membrane-bound complement inhibitor on the cells of freshly prepared and cryopreserved amniotic membrane. Cells of amniotic membrane were separated mechanically. Epithelial and mesenchymal cells were identified by the intracellular expression of nanog and the cell surface ICAM1 positivity, respectively. Multicolor flow cytometric immunophenotyping was used for determination of the CD59 expression. CellQuest-Pro software program (Becton Dickinson) was used both for measurements and analysis. CD59-positive cells could be detected in all investigated samples and in all investigated cell types, although the expression level of CD59 differed. CD59 was expressed both on freshly prepared and frozen-stored samples. Higher level of CD59 was detected on ICAM1+ mesenchymal cells than on nanog+ epithelial cells. Our findings indicate that amniotic membranes maintain their complement inhibiting capacity after cryopreservation.

scholarly journals Phenotyping of Leukocytes and Leukocyte-Derived Extracellular Vesicles

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Lotte Hatting Pugholm ◽  
Rikke Bæk ◽  
Evo Kristina Lindersson Søndergaard ◽  
Anne Louise Schacht Revenfeld ◽  
Malene Møller Jørgensen ◽  
...  
Keyword(s):  
Immune System ◽  
Cell Surface ◽  
Extracellular Vesicles ◽  
Cell Types ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Parent Cell ◽  
Phenotypic Differences ◽  
Immunological Markers ◽  
Cellular Expression

Extracellular vesicles (EVs) have a demonstrated involvement in modulating the immune system. It has been proposed that EVs could be used as biomarkers for detection of inflammatory and immunological disorders. Consequently, it is of great interest to investigate EVs in more detail with focus on immunological markers. In this study, five major leukocyte subpopulations and the corresponding leukocyte-derived EVs were phenotyped with focus on selected immunological lineage-specific markers and selected vesicle-related markers. The leukocyte-derived EVs displayed phenotypic differences in the 34 markers investigated. The majority of the lineage-specific markers used for identification of the parent cell types could not be detected on EVs released from monocultures of the associated cell types. In contrast, the vesicular presentation of CD9, CD63, and CD81 correlated to the cell surface expression of these markers, however, with few exceptions. Furthermore, the cellular expression of CD9, CD63, and CD81 varied between leukocytes present in whole blood and cultured leukocytes. In summary, these data demonstrate that the cellular and vesicular presentation of selected lineage-specific and vesicle-related markers may differ, supporting the accumulating observations that sorting of molecular cargo into EVs is tightly controlled.

scholarly journals ER Stress and Iron Homeostasis: A New Frontier for the UPR

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Susana J. Oliveira ◽  
Maria de Sousa ◽  
Jorge P. Pinto
Keyword(s):  
Cell Surface ◽  
Er Stress ◽  
Conformational Changes ◽  
Iron Homeostasis ◽  
Hereditary Hemochromatosis ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Clinical Value ◽  
Mhc I ◽  
Functional Perspective

The C282Y mutation of HFE accounts for the majority of cases of the iron overload disease Hereditary Hemochromatosis (HH). The conformational changes introduced by this mutation impair the HFE association with β2-microglobulin (β2m) and the cell surface expression of the protein: with two major consequences. From a functional perspective, the ability of HFE to bind to transferrin receptors 1 and 2 is lost in the C282Y mutant, thus affecting hepcidin regulation. Also due to the faulty assembly with β2m, HFE-C282Y molecules remain in the endoplasmic reticulum (ER) as aggregates that undergo proteasomal degradation and activate an Unfolded Protein Response (UPR). UPR activation, regardless of the ER stress stimuli, was shown to reshape the expression profile of iron-related genes and to decrease MHC-I cell surface expression. The possibility of a HFE-C282Y-mediated interplay between the UPR and iron homeostasis influencing disease progression and the clinical heterogeneity among C282Y carriers is discussed. The responsiveness of the ER chaperone calreticulin to both ER and iron-induced oxidative stresses, and its correlation with HH patients’ phenotype, reinforce the interest of dissecting the UPR signaling/iron metabolism crosstalk and points to the potential clinical value of use of pharmacological chaperones in HFE-HH.

scholarly journals Promoter choice and translational repression determine cell type–specific cell surface density of the inhibitory receptor CD85j expressed on different hematopoietic lineages

Blood ◽  
2010 ◽  
Vol 115 (16) ◽  
pp. 3278-3286 ◽  
Author(s):  
David L. Lamar ◽  
Cornelia M. Weyand ◽  
Jörg J. Goronzy
Keyword(s):  
Cell Surface ◽  
Protein Translation ◽  
Cell Types ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Cell Contact ◽  
Specific Cell ◽  
Inhibitory Receptor ◽  
Specific Expression ◽  
Mhc Class Ia

AbstractCD85j (ILT2/LILRB1/LIR-1) is an inhibitory receptor that recognizes major histocompatibility complex (MHC) class Ia and Ib alleles that are widely expressed on all cell types. On ligand recognition, CD85j diminishes kinase activity by recruiting phosphatases to motifs within its cytoplasmic domain. Within the hematopoietic system, CD85j is expressed with cell-specific patterns and cell surface densities that reflect the different roles of cell contact-mediated inhibition in these lineages. While monocytes ubiquitously have high cell surface expression, B lymphocytes start to express CD85j at intermediate levels during early B-cell maturation and natural killer (NK) cells and T cells exhibit a low level of expression on only a subset of cells. The cell-specific expression pattern is accomplished by 2 complementing but not independent mechanisms. Lymphocytes and monocytes use distinct promoters to drive CD85j expression. The lymphocyte promoter maps 13 kilobases (kb) upstream of the monocyte promoter; its use results in the inclusion of a distant exon into the 5′-untranslated region. A short sequence stretch within this exon has the unique function of repressing CD85j protein translation and is responsible for the subdued expression in lymphocytes. These cell-specific mechanisms allow tailoring of CD85j levels to the distinct roles it plays in different hematopoietic lineages.

scholarly journals Primary Sooty Mangabey Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 2 nef Alleles Modulate Cell Surface Expression of Various Human Receptors and Enhance Viral Infectivity and Replication

2005 ◽  
Vol 79 (16) ◽  
pp. 10547-10560 ◽  
Author(s):  
Jan Münch ◽  
Michael Schindler ◽  
Steffen Wildum ◽  
Elke Rücker ◽  
Nicola Bailer ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Surface ◽  
T Cell Activation ◽  
Cell Activation ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Mhc I ◽  
Mhc Ii ◽  
Immunodeficiency Virus

ABSTRACT The nef gene of the pathogenic simian immunodeficiency virus (SIV) mac239 clone has been well characterized. Little is known, however, about the function of nef alleles derived from naturally SIVsm-infected sooty mangabeys (Cercocebus atys) and from human immunodeficiency virus type 2 (HIV-2)-infected individuals. Addressing this, we demonstrate that, similarly to the SIVmac239 nef, primary SIVsm and HIV-2 nef alleles down-modulate cell surface expression of human CD4, CD28, CD3, and class I or II major histocompatibility complex (MHC-I or MHC-II, respectively) molecules, up-regulate surface expression of the invariant chain (Ii) associated with immature MHC-II, inhibit early T-cell activation events, and enhance virion infectivity. Both also stimulate viral replication, although HIV-2 nef alleles were less active in this assay than SIVsm nef alleles. Mutational analysis showed that a dileucine-based sorting motif in the C-proximal loop of SIV or HIV-2 Nef is critical for its effects on CD4, CD28, and Ii but dispensable for down-regulation of CD3, MHC-I, and MHC-II. The C terminus of SIV and HIV-2 Nef was exclusively required for down-modulation of MHC-I, further demonstrating that analogous functions are mediated by different domains in Nef proteins derived from different groups of primate lentiviruses. Our results demonstrate that none of the eight Nef functions investigated had been newly acquired after cross-species transmission of SIVsm from naturally infected mangabeys to humans or macaques. Notably, HIV-2 and SIVsm nef alleles efficiently down-modulate CD3 and C28 surface expression and inhibit T-cell activation more efficiently than HIV-1 nef alleles. These differences in Nef function might contribute to the relatively low levels of immune activation observed in HIV-2-infected human individuals.

scholarly journals Differential Regulation of Dk and KkMajor Histocompatibility Complex Class I Proteins on the Cell Surface after Infection of Murine Cells by Pseudorabies Virus

1999 ◽  
Vol 73 (7) ◽  
pp. 5748-5756 ◽  
Author(s):  
R. L. Sparks-Thissen ◽  
L. W. Enquist
Keyword(s):  
Cell Surface ◽  
Gene Product ◽  
Mhc Class I ◽  
Pseudorabies Virus ◽  
Surface Expression ◽  
Early Gene ◽  
Class I ◽  
Cell Surface Expression ◽  
Histocompatibility Complex ◽  
The Individual

ABSTRACT After pseudorabies virus (PRV) infection of murine L929 cells, the cell surface expression of major histocompatibility complex (MHC) class I proteins changes such that the total amount of MHC class I molecules remains relatively constant but the levels of the individual alleles Dk and Kk vary. This is an active process involving at least three PRV gene products that act in an allele-specific manner such that cell surface expression of MHC class I Dk is decreased and that of Kk is increased. Our results indicate that an early gene product mediates the overall reduction in Dk protein and a late gene product which is mutant in the attenuated PRV strain Bartha mediates the increase in Kk protein. We provide additional evidence for a third gene product involved in the regulation of the synthesis of both the Dk and Kk proteins. In addition, we show that the early decrease in the Dk protein is not due to a block in synthesis or processing of the complex through the secretory system.

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