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https://www.readbyqxmd.com/read/28533221/cd9-regulates-mhc-ii-trafficking-in-monocyte-derived-dendritic-cells
#1
Vera Rocha-Perugini, Gloria Martínez Del Hoyo, José Maria González-Granado, Marta Ramírez-Huesca, Virginia Zorita, Eric Rubinstein, Claude Boucheix, Francisco Sánchez-Madrid
Antigen presentation by dendritic cells (DCs) stimulates naïve CD4(+) T cells, triggering T cell activation and the adaptive arm of the immune response. Newly synthesized major histocompatibility complex class II molecules (MHC-II) accumulate at MHC-II-enriched endosomal compartments, and are transported to the plasma membrane of DCs after binding to antigenic peptides to enable antigen presentation. In DCs, MHC-II molecules are included in tetraspanin-enriched microdomains (TEMs). However, the role of tetraspanin CD9 in these processes remains largely undefined...
May 22, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28530714/cd8%C3%AE-%C3%AE-intraepithelial-lymphocytes-arise-from-two-main-thymic-precursors
#2
Roland Ruscher, Rebecca L Kummer, You Jeong Lee, Stephen C Jameson, Kristin A Hogquist
TCRαβ(+)CD4(-)CD8α(+)CD8β(-) intestinal intraepithelial lymphocytes (CD8αα IELs) are an abundant population of thymus-derived T cells that protect the gut barrier surface. We sought to better define the thymic IEL precursor (IELp) through analysis of its maturation, localization and emigration. We defined two precursor populations among TCRβ(+)CD4(-)CD8(-) thymocytes by dependence on the kinase TAK1 and rigorous lineage-exclusion criteria. Those IELp populations included a nascent PD-1(+) population and a T-bet(+) population that accumulated with age...
May 22, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28530396/the-hydrotropic-action-of-cationic-hydrotrope-p-toluidinium-chloride-on-the-solubility-of-sparingly-soluble-gliclazide-drug-molecule-a-computational-study
#3
Shubhadip Das, Sandip Paul
We perform classical molecular dynamics simulations of sparingly soluble drug gliclazide (GLC) and hydrotrope p-toluidinium chloride (PTOL) in water with a regime of PTOL concentrations. Our results demonstrate that PTOL starts to self aggregate above its minimum hydrotrope concentration (MHC). Further these PTOL aggregates create a mixed micellar like framework in which the hydrophobic small tail part of most of the PTOL molecules direct towards the inside whereas in order to make favorable contact with water molecules its hydrophilic ammonium group points outward...
May 22, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28529511/characterization-of-cd4-t-cell-epitopes-of-infliximab-and-rituximab-identified-from-healthy-donors
#4
Moustafa Hamze, Sylvain Meunier, Anette Karle, Abdelaziz Gdoura, Amélie Goudet, Natacha Szely, Marc Pallardy, Franck Carbonnel, Sebastian Spindeldreher, Xavier Mariette, Corinne Miceli-Richard, Bernard Maillère
The chimeric antibodies anti-CD20 rituximab (Rtx) and anti-TNFα infliximab (Ifx) induce antidrug antibodies (ADAs) in many patients with inflammatory diseases. Because of the key role of CD4 T lymphocytes in the initiation of antibody responses, we localized the CD4 T cell epitopes of Rtx and Ifx. With the perspective to anticipate immunogenicity of therapeutic antibodies, identification of the CD4 T cell epitopes was performed using cells collected in healthy donors. Nine T cell epitopes were identified in the variable chains of both antibodies by deriving CD4 T cell lines raised against either Rtx or Ifx...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28528220/properties-of-the-tapasin-homologue-tapbpr
#5
REVIEW
Andreas Neerincx, Louise H Boyle
The presentation of antigenic peptides by MHC class I molecules plays a vital role in generating T cell responses against infection and cancer. Over the last two decades the central role of tapasin as a peptide editor that influences the loading and optimisation of peptides onto MHC class I molecules has been extensively characterised. Recently, it has become evident that the tapasin-related protein, TAPBPR, functions as a second peptide editor which influences the peptides displayed by MHC class I molecules...
May 18, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28526413/tcr-crosslinking-promotes-crk-adaptor-protein-binding-to-tyrosine-phosphorylated-cd3%C3%AE-chain
#6
Guangyu Dong, Rachel Kalifa, Pulak Ranjan Nath, Sigal Gelkop, Noah Isakov
T cell antigen receptor (TCR) binding of a peptide antigen presented by antigen-presenting cells (APCs) in the context of surface MHC molecules initiates signaling events that regulate T cell activation, proliferation and differentiation. A key event in the activation process is the phosphorylation of the conserved tyrosine residues within the CD3 chain immunoreceptor tyrosine-based activation motifs (ITAMs), which operate as docking sites for SH2 domain-containing effector proteins. Phosphorylation of the CD3ζ ITAMs renders the CD3 chain capable of binding the ζ-chain associated protein 70 kDa (ZAP70), a protein tyrosine kinase that is essential for T cell activation...
May 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28521800/immunogenicity-and-immunomodulatory-effects-of-the-human-chondrocytes-hchonj
#7
Chae-Lyul Lim, Yeon-Ju Lee, Jong-Ho Cho, Heonsik Choi, Bumsup Lee, Myung Chul Lee, Sujeong Kim
BACKGROUND: Invossa™ (TissueGene-C) is a cell and gene therapy for osteoarthritis. It is composed of primary human chondrocytes (hChonJ cells) and irradiated human chondrocytes modified to express TGF-β1 (hChonJb#7 cells). The hChonJ cells were isolated from a polydactyly donor, and TGF-β1 cDNA was delivered to the cells, generating hChonJb#7 cells. Since the cells are allogeneic, the concern of immune response against cells has been raised. In this study, we investigated the immunogenicity of allogenic human chondrocyte, hChonJ cells...
May 18, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28521747/insights-into-the-ancestral-organisation-of-the-mammalian-mhc-class-ii-region-from-the-genome-of-the-pteropid-bat-pteropus-alecto
#8
Justin H J Ng, Mary Tachedjian, Lin-Fa Wang, Michelle L Baker
BACKGROUND: Bats are an extremely successful group of mammals and possess a variety of unique characteristics, including their ability to co-exist with a diverse range of pathogens. The major histocompatibility complex (MHC) is the most gene dense and polymorphic region of the genome and MHC class II (MHC-II) molecules play a vital role in the presentation of antigens derived from extracellular pathogens and activation of the adaptive immune response. Characterisation of the MHC-II region of bats is crucial for understanding the evolution of the MHC and of the role of pathogens in shaping the immune system...
May 18, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28518215/the-tlr9-signaling-pathway-regulates-mr1-mediated-bacterial-antigen-presentation-in-b-cells
#9
Jianyun Liu, Randy R Brutkiewicz
Mucosal-associated invariant T (MAIT) cells are conserved T cells that express a semi-invariant TCR (Vα7.2 in humans and Vα19 in mice). The development of MAIT cells requires the antigen (Ag) presenting MHC-related protein 1 (MR1), as well as commensal bacteria. The mechanisms that regulate the functional expression of MR1 molecules and their loading with bacterial Ag in APCs are largely unknown. We have found that treating B cells with the TLR9 agonist CpG increases MR1 surface expression. Interestingly, activation of TLR9 by CpG-A (but not CpG-B) enhances MR1 surface expression...
May 18, 2017: Immunology
https://www.readbyqxmd.com/read/28518056/functionally-diverse-human-t-cells-recognize-non-microbial-antigens-presented-by-mr1
#10
Marco Lepore, Artem Kalinichenko, Salvatore Calogero, Pavanish Kumar, Bhairav Paleja, Mathias Schmaler, Vipin Narang, Francesca Zolezzi, Michael Poidinger, Lucia Mori, Gennaro De Libero
MHC class I-related molecule MR1 presents riboflavin- and folate-related metabolites to mucosal-associated invariant T cells, but it is unknown whether MR1 can present alternative antigens to other T cell lineages. In healthy individuals we identified MR1-restricted T cells (named MR1T cells) displaying diverse TCRs and reacting to MR1-expressing cells in the absence of microbial ligands. Analysis of MR1T cell clones revealed specificity for distinct cell-derived antigens and alternative transcriptional strategies for metabolic programming, cell cycle control and functional polarization following antigen stimulation...
May 18, 2017: ELife
https://www.readbyqxmd.com/read/28515356/licensing-delineates-helper-and-effector-nk-cell-subsets-during-viral-infection
#11
Anthony E Zamora, Ethan G Aguilar, Can M Sungur, Lam T Khuat, Cordelia Dunai, G Raymond Lochhead, Juan Du, Claire Pomeroy, Bruce R Blazar, Dan L Longo, Jeffrey M Venstrom, Nicole Baumgarth, William J Murphy
Natural killer (NK) cells can be divided into phenotypic subsets based on expression of receptors that bind self-MHC-I molecules, a concept termed licensing or education. Here we show NK cell subsets with different migratory, effector, and immunoregulatory functions in dendritic cell and antigen (ag)-specific CD8+ T cell responses during influenza and murine cytomegalovirus infections. Shortly after infection, unlicensed NK cells localized in draining lymph nodes and produced GM-CSF, which correlated with the expansion and activation of dendritic cells, and resulted in greater and sustained ag-specific T cell responses...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28511928/rational-design-of-nanoparticles-towards-targeting-antigen-presenting-cells-and-improved-t-cell-priming
#12
Eva Zupančič, Caterina Curato, Maria Paisana, Catarina Rodrigues, Ziv Porat, Ana S Viana, Carlos A M Afonso, João Pinto, Rogério Gaspar, João N Moreira, Ronit Satchi-Fainaro, Steffen Jung, Helena F Florindo
Vaccination is a promising strategy to trigger and boost immune responses against cancer or infectious disease. We have designed, synthesized and characterized aliphatic-polyester (poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) to investigate how the nature of protein association (adsorbed versus entrapped) and polymer/surfactant concentrations impact on the generation and modulation of antigen-specific immune responses. The ability of the NP formulations to target dendritic cells (DC), be internalized and activate the T cells was characterized and optimized in vitro and in vivo using markers of DC activation and co-stimulatory molecules...
May 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28509875/in-silico-analysis-of-epitope-based-vaccine-candidates-against-hepatitis-b-virus-polymerase-protein
#13
Juzeng Zheng, Xianfan Lin, Xiuyan Wang, Liyu Zheng, Songsong Lan, Sisi Jin, Zhanfan Ou, Jinming Wu
Hepatitis B virus (HBV) infection has persisted as a major public health problem due to the lack of an effective treatment for those chronically infected. Therapeutic vaccination holds promise, and targeting HBV polymerase is pivotal for viral eradication. In this research, a computational approach was employed to predict suitable HBV polymerase targeting multi-peptides for vaccine candidate selection. We then performed in-depth computational analysis to evaluate the predicted epitopes' immunogenicity, conservation, population coverage, and toxicity...
May 16, 2017: Viruses
https://www.readbyqxmd.com/read/28508576/mhc-i-presentation-of-toxoplasma-gondii-immunodominant-antigen-does-not-require-sec-22b-and-is-regulated-by-antigen-orientation-at-the-vacuole-membrane
#14
Célia Buaillon, Nestor A Guerrero, Ignacio Cebrian, Sophie Blanié, Jodie Lopez, Emilie Bassot, Virginie Vasseur, Julien Santi-Rocca, Nicolas Blanchard
The intracellular Toxoplasma gondii parasite replicates within a parasitophorous vacuole (PV). T. gondii secretes proteins that remain soluble in the PV space, are inserted into PV membranes or are exported beyond the PV boundary. In addition to supporting T. gondii growth, these proteins can be processed and presented by MHC I for CD8(+) T-cell recognition. Yet it is unclear whether membrane binding influences the processing pathways employed and if topology of membrane antigens impacts their MHC I presentation...
May 15, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28507791/the-mutational-status-of-p53-can-influence-its-recognition-by-human-t-cells
#15
Katerina Shamalov, Shlomo N Levy, Miryam Horovitz-Fried, Cyrille J Cohen
p53 was reported to be an attractive immunotherapy target because it is mutated in approximately half of human cancers, resulting in its inactivation and often accumulation in tumor cells. Peptides derived from p53 are presented by class I MHC molecules and may act as tumor-associated epitopes which could be targeted by p53-specific T cells. Interestingly, it was recently shown that there is a lack of significant correlation between p53 expression levels in tumors and their recognition by p53-TCR transduced T cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28502107/a-nano-particle-vector-comprised-of-poly-lactic-co-glycolic-acid-and-monophosphoryl-lipid-a-and-recombinant-mycobacterium-avium-subsp-paratuberculosis-peptides-stimulate-a-pro-immune-profile-in-bovine-macrophages
#16
Cleverson D Souza, John P Bannantine, Wendy C Brown, M Grant Norton, William C Davis, Julianne K Hwang, Parissa Ziaei, Gaber S Abdellrazeq, Meaghan V Eren, James R Deringer, Elizabeth Laws, Maria Clara D Cardieri
AIMS: We evaluated the potential of a nanoparticle (NP) delivery system to improve methods of delivery of candidate peptide based vaccines for Paratuberculosis in cattle. METHODS AND RESULTS: Peptides derived from Mycobacterium avium subsp paratuberculosis (Map), and the proinflammatory monophosphoryl lipid A (MPLA) were incorporated in polymeric NPs based on poly (D, L-lactide-co-glycolide) (PLGA). The PLGA/MPLA NPs carriers were incubated with macrophages to examine their effects on survival and function...
May 14, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/28501913/chronic-myeloid-leukemia-immunobiology-and-novel-immunotherapeutic-approaches
#17
Emilie Cayssials, Francois Guilhot
Imatinib has revolutionized the treatment and prognosis of chronic myeloid leukemia (CML) with survival rates now approaching those of the age-matched healthy population. To be able to discontinue tyrosine kinase inhibitor (TKI) treatment, it is necessary to develop complementary therapies to target minimal residual disease. Recent findings by a number of investigators in both CML mouse models and CML patients offer evidence that many factors in the leukemic microenvironment can collectively contribute to immune escape, including expansion of myeloid-derived suppressor cells, programmed death-1/programmed death-1 ligand interactions resulting in T-cell impairment, expression of soluble suppressive factors such as soluble CD25, and down-regulation of MHC molecules by CML cells...
May 13, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/28497030/fda-approved-immunosuppressants-targeting-staphylococcal-superantigens-mechanisms-and-insights
#18
REVIEW
Teresa Krakauer
Immunostimulating staphylococcal enterotoxin B (SEB) and related superantigenic toxins cause diseases in human beings and laboratory animals by hyperactivating cells of the immune system. These protein toxins bind to the major histocompatibility complex class II (MHC II) molecules and specific Vβ regions of T-cell receptors (TCRs), resulting in the stimulation of both monocytes/macrophages and T lymphocytes. The bridging of TCR with MHC II molecules by superantigens triggers intracellular signaling cascades, resulting in excessive release of proinflammatory mediators and massive polyclonal T-cell proliferation...
2017: ImmunoTargets and Therapy
https://www.readbyqxmd.com/read/28495591/the-hla-dr-mediated-signalling-increases-the-migration-and-invasion-of-melanoma-cells-the-expression-and-lipid-raft-recruitment-of-adhesion-receptors-pd-l1-and-signal-transduction-proteins
#19
Francesca Costantini, Giovanna Barbieri
The constitutive expression of Major Histocompatibility Complex (MHC) class II molecules is restricted to professional Antigen-Presenting Cells (APCs), nevertheless almost 50% of melanomas express constitutively the MHC class II molecules. Therefore, in two MHC class II constitutive expressing melanoma cell lines we studied the signalling mediated by the HLA-DR molecules in the aim to understand the consequence of class II mediated signalling on metastatic dissemination of melanoma. In particular, we reported that the HLA-DR mediated signalling play a new role in melanoma progression, increasing the migration and invasion of melanoma cells...
May 8, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28494326/mait-cells-and-mr1-antigen-recognition
#20
REVIEW
Andrew N Keller, Alexandra J Corbett, Jacinta M Wubben, James McCluskey, Jamie Rossjohn
Mucosal-associated invariant T cells (MAIT cells) are innate-like T cells that recognise antigens presented by the monomorphic MHC-I related molecule, MR1. Distinct from the conventional MHC-restricted T cell system, MR1 presents small-molecule precursors, derived from microbial biosynthesis of riboflavin, to activate the innate MAIT cell effector potential. Recent data demonstrates how: vitamin B precursors modulate intracellular trafficking of MR1 and impact on MAIT cell development; variation in the MAIT cell antigen receptor sequence impacts MR1-antigen recognition; and most notably, how MR1 can capture chemical identities distinct from riboflavin precursors, including drugs and drug-like molecules...
May 8, 2017: Current Opinion in Immunology
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