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https://www.readbyqxmd.com/read/29351991/differing-roles-of-cd1d2-and-cd1d1-proteins-in-type-i-natural-killer-t-cell-development-and-function
#1
Srinivasan Sundararaj, Jingjing Zhang, S Harsha Krovi, Romain Bedel, Kathryn D Tuttle, Natacha Veerapen, Gurdyal S Besra, Yogesh Khandokar, T Praveena, Jérôme Le Nours, Jennifer L Matsuda, Jamie Rossjohn, Laurent Gapin
MHC class I-like CD1 molecules have evolved to present lipid-based antigens to T cells. Differences in the antigen-binding clefts of the CD1 family members determine the conformation and size of the lipids that are presented, although the factors that shape CD1 diversity remain unclear. In mice, two homologous genes, CD1D1 and CD1D2, encode the CD1d protein, which is essential to the development and function of natural killer T (NKT) cells. However, it remains unclear whether both CD1d isoforms are equivalent in their antigen presentation capacity and functions...
January 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29345060/porcine-nk-cells-display-features-associated-with-antigen-presenting-cells
#2
Steffi De Pelsmaeker, Bert Devriendt, Georges Leclercq, Herman W Favoreel
NK cells are members of the innate immunity and play a central role in the defense against viral infections and cancer development, but also contribute to triggering and shaping adaptive immune responses. Human NK cells may express MHC II and costimulatory molecules, including CD86, CD80, and OX40 ligand, which allows them to stimulate the CD4+ T-cell response. In contrast, murine NK cells do not express MHC II or costimulatory molecules. Upon activation, mouse NK cells can acquire these molecules from dendritic cells (DCs) via intercellular membrane transfer, which leads to suppression of DC-induced CD4+ T-cell responses rather than stimulation of T-cell responses...
January 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29341118/inhibition-of-the-fgl2-fc%C3%AE-riib-riii-immunosuppressive-pathway-enhances-antiviral-t-cell-and-b-cell-responses-leading-to-clearance-of-lcmv-cl-13
#3
Olga Klingberg, Ramzi Khattar, Kaveh Farrokhi, Dario Ferri, Nataliya Yavorska, Jianhua Zhang, Hassan Sadozai, Oyedele Adeyi, Andrzej Chruscinski, Gary A Levy, Nazia Selzner
Persistent viruses evade immune detection by interfering with virus-specific innate and adaptive antiviral immune responses. Fibrinogen-Like Protein-2 (FGL2) is a potent effector molecule of CD4+ CD25+ FoxP3+ regulatory T cells (Treg) and exerts its immunosuppressive activity following ligation to its cognate receptor, FcγRIIB/RIII. The role of FGL2 in the pathogenesis of chronic viral infection caused by Lymphocytic Choriomeningitis Virus Clone-13 (LCMV cl-13) was assessed in this study. Chronically infected fgl2+/+ mice had increased plasma levels of FGL2, with reduced expression of the maturation markers, CD80, CD86 and MHC-II on macrophages and dendritic cells (DC) and impaired production of neutralizing antibody...
January 17, 2018: Immunology
https://www.readbyqxmd.com/read/29331322/expression-level-of-risk-genes-of-mhc-class-ii-is-a-susceptibility-factor-for-autoimmunity-new-insights
#4
REVIEW
Carmen Gianfran, Laura Pisapia, Stefania Picascia, Maria Strazzullo, Giovanna Del Pozzo
To date, the study of the impact of major hystocompatibility complex on autoimmunity has been prevalently focused on structural diversity of MHC molecules in binding and presentation of (auto)antigens to cognate T cells. Recently, a number of experimental evidences suggested new points of view to investigate the complex relationships between MHC gene expression and the individual predisposition to autoimmune diseases. Irrespective of the nature of the antigen, a threshold of MHC-peptide complexes needs to be reached, as well as a threshold of T cell receptors engaged is required, for the activation and proliferation of autoantigen-reactive T cells...
January 10, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29330322/cutting-edge-piezo1-mechanosensors-optimize-human-t-cell-activation
#5
Chinky Shiu Chen Liu, Deblina Raychaudhuri, Barnali Paul, Yogaditya Chakrabarty, Amrit Raj Ghosh, Oindrila Rahaman, Arindam Talukdar, Dipyaman Ganguly
TCRs recognize peptides on MHC molecules and induce downstream signaling, leading to activation and clonal expansion. In addition to the strength of the interaction of TCRs with peptides on MHC molecules, mechanical forces contribute to optimal T cell activation, as reflected by the superior efficiency of immobilized TCR-cross-linking Abs compared with soluble Abs in TCR triggering, although a dedicated mechanotransduction module is not identified. We found that the professional mechanosensor protein Piezo1 is critically involved in human T cell activation...
January 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29327813/computational-tools-for-the-identification-and-interpretation-of-sequence-motifs-in-immunopeptidomes
#6
REVIEW
Bruno Alvarez, Carolina Barra, Morten Nielsen, Massimo Andreatta
Recent advances in proteomics and mass-spectrometry have widely expanded the detectable peptide repertoire presented by major histocompatibility complex (MHC) molecules on the cell surface, collectively known as the immunopeptidome. Finely characterizing the immunopeptidome brings about important basic insights into the mechanisms of antigen presentation, but can also reveal promising targets for vaccine development and cancer immunotherapy. In this report, we describe a number of practical and efficient approaches to analyze immunopeptidomics data, discussing the identification of meaningful sequence motifs in various scenarios and considering current limitations...
January 12, 2018: Proteomics
https://www.readbyqxmd.com/read/29324305/caveolin-mediated-endocytosis-of-the-chlamydia-m278-outer-membrane-peptide-encapsulated-in-poly-lactic-acid-poly-ethylene-glycol-nanoparticles-by-mouse-primary-dendritic-cells-enhances-specific-immune-effectors-mediated-by-mhc-class-ii-and-cd4-t-cells
#7
Saurabh Dixit, Rajnish Sahu, Richa Verma, Skyla Duncan, Guillermo H Giambartolomei, Shree R Singh, Vida A Dennis
We previously developed a Chlamydia trachomatis nanovaccine (PPM) by encapsulating a chlamydial M278 peptide within poly(lactic acid)-poly(ethylene glycol) biodegradable nanoparticles that immunopotentiated Chlamydia-specific immune effector responses in mice. Herein, we investigated the mechanistic interactions of PPM with mouse bone marrow-derived dendritic cells (DCs) for its uptake, trafficking, and T cell activation. Our results reveal that PPM triggered enhanced expression of effector cytokines and chemokines, surface activation markers (Cd1d2, Fcgr1), pathogen-sensing receptors (TLR2, Nod1), co-stimulatory (CD40, CD80, CD86) and MHC class I and II molecules...
December 26, 2017: Biomaterials
https://www.readbyqxmd.com/read/29315598/improved-methods-for-predicting-peptide-binding-affinity-to-mhc-class-ii-molecules
#8
Kamilla Kjaergaard Jensen, Massimo Andreatta, Paolo Marcatili, Søren Buus, Jason A Greenbaum, Zhen Yan, Alessandro Sette, Bjoern Peters, Morten Nielsen
Major histocompatibility complex class II (MHC-II) molecules are expressed on the surface of professional antigen presenting cells where they display peptides to T helper cells, which orchestrate the onset and outcome of many host immune responses. Understanding which peptides will be presented by the MHC-II molecule is therefore important for understanding the activation of T helper cells and can be used to identify T-cell epitopes. We here present updated versions of two MHC class II peptide binding affinity prediction methods, NetMHCII and NetMHCIIpan...
January 6, 2018: Immunology
https://www.readbyqxmd.com/read/29313030/poly-2-propylacrylic-acid-poly-lactic-co-glycolic-acid-blend-microparticles-as-a-targeted-antigen-delivery-system-to-direct-either-cd4-or-cd8-t-cell-activation
#9
Lirong Yang, Evelyn Bracho-Sanchez, Lawrence P Fernando, Jamal S Lewis, Matthew R Carstens, Craig L Duvall, Benjamin G Keselowsky
Poly(lactic-co-glycolic acid) (PLGA) based microparticles (MPs) are widely investigated for their ability to load a range of molecules with high efficiency, including antigenic proteins, and release them in a controlled manner. Micron-sized PLGA MPs are readily phagocytosed by antigen presenting cells, and localized to endosomes. Due to low pH and digestive enzymes, encapsulated protein cargo is largely degraded and processed in endosomes for MHC-II loading and presentation to CD4+ T cells, with very little antigen delivered into the cytosol, limiting MHC-I antigenic loading and presentation to CD8+ T cells...
June 2017: Bioengineering & Translational Medicine
https://www.readbyqxmd.com/read/29311365/simultaneous-recognition-of-allogeneic-mhc-and-cognate-autoantigen-by-autoreactive-t-cells-in-transplant-rejection
#10
Adam L Burrack, Laurie G Landry, Janet Siebert, Marilyne Coulombe, Ronald G Gill, Maki Nakayama
The autoimmune condition is a primary obstacle to inducing tolerance in type 1 diabetes patients receiving allogeneic pancreas transplants. It is unknown how autoreactive T cells that recognize self-MHC molecules contribute to MHC-disparate allograft rejection. In this report, we show the presence and accumulation of dual-reactive, that is autoreactive and alloreactive, T cells in C3H islet allografts that were transplanted into autoimmune diabetic NOD mice. Using high-throughput sequencing, we discovered that T cells prevalent in allografts share identical TCRs with autoreactive T cells present in pancreatic islets...
January 8, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29311245/both-mhc-class-i-and-class-ii-molecules-are-required-while-mhc-i-appears-to-play-a-critical-role-in-host-defense-against-primary-coxiella-burnetii-infection
#11
Laura Buttrum, Lindsey Ledbetter, Rama Cherla, Yan Zhang, William J Mitchell, Guoquan Zhang
To understand the role of class I major histocompatibility complex (MHC-I) and class II MHC (MHC-II) antigen presentation pathways in host defense against C. burnetii infection, we examined if MHC-I or MHC-II deficiency in mice would significantly influence their susceptibility to virulent C. burnetii Nine Mile phase I (NMI) infection. The results indicate that NMI infection induced more severe disease in both MHC-I deficient and MHC-II deficient mice compared to WT mice, while only MHC-I deficient mice developed a severe persistent infection and were unable to control bacterial replication...
January 8, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29305065/high-macrophage-pd-l1-expression-not-responsible-for-t-cell-suppression
#12
Naomi Goldman, Yelizavet D Lomakova, Jennifer Londregan, Amanda Bucknum, Kelley DePierri, John Somerville, James E Riggs
Tumors are often comprised of microenvironments (TMEs) with a high proportion of cells and molecules that regulate immunity. Peritoneal cavity (PerC) cell culture reproduces key features of TMEs as lymphocyte proliferation is suppressed by PerC macrophages (Mϕs). We monitored the expression of T cell stimulatory (Class II MHC, B7) and inhibitory (PD-L1) molecules by PerC APCs before and after culture and report here that IFNγ-driven PD-L1 expression increased markedly on PerC Mϕs after TCR ligation, even more so than seen with direct APC activation by LPS...
December 30, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/29302256/heterogeneous-nuclear-ribonucleoprotein-a2b1-exerts-a-regulatory-role-in-lipopolysaccharide-stimulated-38b9-b-cell-activation
#13
Jisang Park, Chung-Hyeon Choe, Ju Kim, Jing Shian Yang, Jin Hyun Kim, Hyonseok Jang, Yong-Suk Jang
Major histocompatibility complex (MHC) class II molecules, which are recognized for their primary function of presenting an antigen to the T cell receptor, are involved in various signaling pathways in B cell activation. We identified heterogeneous nuclear ribonucleoprotein (hnRNP) A2B1 as an MHC class II molecule-associated protein involved in MHC class II-mediated signal transduction in lipopolysaccharide (LPS)-stimulated 38B9 B cells. Although the function of hnRNP A2B1 in the nucleus is primarily known, the level of hnRNP A2B1 in the cytoplasm was increased in LPS-stimulated 38B9 cells, while it was not detected in the cytoplasm of non-treated 38B9 cells...
December 2017: Immune Network
https://www.readbyqxmd.com/read/29298343/epcam-peptide-primed-dendritic-cell-vaccination-confers-significant-anti-tumor-immunity-in-hepatocellular-carcinoma-cells
#14
Yoo Jin Choi, Seong-Joon Park, You-Soo Park, Hee Sung Park, Kwang Mo Yang, Kyu Heo
Cancer stem-like cells (CSCs) may play a key role in tumor initiation, self-renewal, differentiation, and resistance to current treatments. Dendritic cells (DCs) play a vital role in host immune reactions as well as antigen presentation. In this study, we explored the suitability of using CSC peptides as antigen sources for DC vaccination against human breast cancer and hepatocellular carcinoma (HCC) with the aim of achieving CSC targeting and enhancing anti-tumor immunity. CD44 is used as a CSC marker for breast cancer and EpCAM is used as a CSC marker for HCC...
2018: PloS One
https://www.readbyqxmd.com/read/29297233/deficiency-of-autoimmune-regulator-impairs-the-immune-tolerance-effect-of-bone-marrow-derived-dendritic-cells-in-mice
#15
Feifei Huo, Dongbei Li, Bo Zhao, Yadong Luo, Bingjie Zhao, Xueyang Zou, Yi Li, Wei Yang
As a transcription factor, autoimmune regulator (Aire) participates in thymic negative selection and maintains immune tolerance mainly by regulating the ectopic expression of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs). Aire is also expressed in dendritic cells (DCs). DCs are professional antigen-presenting cells (APCs) that affect the differentiation of T cells toward distinct subpopulations and participate in the immune response and tolerance, thereby playing an important role in maintaining homeostasis...
January 3, 2018: Autoimmunity
https://www.readbyqxmd.com/read/29296823/mature-murine-megakaryocytes-present-antigen-mhc-class-i-molecules-to-t-cells-and-transfer-them-to-platelets
#16
Anne Zufferey, Edwin R Speck, Kellie R Machlus, Rukhsana Aslam, Li Guo, Mark J McVey, Michael Kim, Rick Kapur, Eric Boilard, Joseph E Italiano, John W Semple
Megakaryocytes (MKs) are bone marrow-derived cells that are primarily responsible for generating platelets for the maintenance of hemostasis. Although MK can variably express major histocompatibility complex (MHC) class I and II molecules during their differentiation, little is known whether they can elicit nonhemostatic immune functions such as T-cell activation. Here, we demonstrate that mature CD34- MHC class II- CD41+ MKs can endocytose exogenous ovalbumin (OVA) and proteolytically generate its immunogenic peptide ligand, which is crosspresented on their surface in association with MHC class I molecules...
September 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29287601/mtor-inhibition-improves-the-immunomodulatory-properties-of-human-bone-marrow-mesenchymal-stem-cells-by-inducing-cox-2-and-pge2
#17
Binsheng Wang, Yu Lin, Yongxian Hu, Wei Shan, Senquan Liu, Yulin Xu, Hao Zhang, Shuyang Cai, Xiaohong Yu, Zhen Cai, He Huang
BACKGROUND: Bone marrow mesenchymal stem cells (MSCs) are promising candidates for the treatment of various inflammatory disorders due to their profound immunomodulatory properties. However, the immunosuppressive capacity of MSCs needs activation by an inflammatory microenvironment, which may negatively impact the therapeutic effect because of increased immunogenicity. Here we explore the role of mammalian target of rapamycin (mTOR) signaling on the immunosuppressive capacity of MSCs, and its impact on immunogenicity in the inflammatory microenvironment...
December 29, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29286392/overlapping-peptide-library-to-map-qa-1-epitopes-in-a-protein
#18
Yi Xu, Samiksha Wasnik, David J Baylink, Edmundo Carreon Berumen, Xiaolei Tang
Qa-1 (HLA-E in human) belongs to a group of non-classical major histocompatibility complex 1b (MHC-Ib) molecules. Recent data suggest that Qa-1 molecules play important roles in surveying cells for structural and functional integrity, inducing immune regulation, and limiting immune responses to viral infections. Additionally, functional augmentation of Qa-1-restricted CD8+ T cells through epitope immunization has shown therapeutic effects in several autoimmune disease animal models, e.g. experimental allergic encephalomyelitis, collagen-induced arthritis, and non-obese diabetes...
December 20, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29285934/synthetic-polymeric-mixed-micelles-target-to-lymph-node-triggering-enhanced-cellular-and-humoral-immune-responses
#19
Chenxi Li, Xiaoxu Zhang, Qing Chen, Jiulong Zhang, Wenpan Li, Haiyang Hu, Xiuli Zhao, Mingxi Qiao, Dawei Chen
It has been widely accepted that lymph nodes (LNs) are critical targets of cancer vaccines since antigen presentation and initiation of T cell-mediated immune responses occur primarily at these locations. In this study, amphiphilic diblock copolymer PEOz-PLA combined with carboxylterminalted-Pluronic F127 were used to construct mixed micelles (carboxylated-NPs) for co-delivery of antigen OVA and Toll-like receptor-7 agonist CL264 (carboxylated-NPs/OVA/CL264) to the LN resident DCs. The results showed that the small, sub-60nm size of the self-assembled mixed micelles enables them to rapidly penetrate into lymphatic vessels and reach DLNs after subcutaneous injection...
December 29, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29285385/mhc-class-ii-associated-stomach-cancer-mutations-correlate-with-lack-of-subsequent-tumor-development
#20
John M Yavorski, George Blanck
The role of tumor cell expression of major histocompatibility class II (MHCII) has been controversial, with evidence indicating that tumor cell expression of MHCII may lead to an anti-tumor immune response and to tumor cell apoptosis and that MHCII has pro-tumorigenic functions. The cancer genome atlas (TCGA) indicates numerous deleterious mutations for the highly specific, MHCII transcriptional activation proteins, RFX5, RFXAP, RFXANK and CIITA. Also, mutations in the non-polymorphic, human leukocyte antigen (HLA)-DRA gene, which encodes the heavy chain for the most prominent human MHCII molecule, HLA-DR, are common...
December 2017: Molecular and Clinical Oncology
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