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https://www.readbyqxmd.com/read/29782520/polymorphic-sites-preferentially-avoid-co-evolving-residues-in-mhc-class-i-proteins
#1
Linda Dib, Nicolas Salamin, David Gfeller
Major histocompatibility complex class I (MHC-I) molecules are critical to adaptive immune defence mechanisms in vertebrate species and are encoded by highly polymorphic genes. Polymorphic sites are located close to the ligand-binding groove and entail MHC-I alleles with distinct binding specificities. Some efforts have been made to investigate the relationship between polymorphism and protein stability. However, less is known about the relationship between polymorphism and MHC-I co-evolutionary constraints...
May 21, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29778202/porcine-monocyte-derived-dendritic-cells-can-be-differentially-activated-by-vesicular-stomatitis-virus-and-its-matrix-protein-mutants
#2
Guoyan Sun, Xinkui Fang, Hao Wu, Xinchu Zhou, Yong Ke, Tao Sun
Vesicular stomatitis virus (VSV) can cause serious vesicular lesions in pigs, and the matrix (M) protein is its predominant virulence factor. Dendritic cells (DCs) act as the bridge between innate and adaptive immune responses. However, the susceptibility of porcine DCs to VSV infection and the role of M protein in modulating the function of infected DCs are still poorly defined. Thus, this study aimed to determine the ability of virulent wild-type VSV(wtVSV) and two attenuated M protein variants (VSVΔM51 and VSVMT ) to induce maturation of porcine monocyte-derived DCs (MoDCs) in vitro...
June 2018: Veterinary Microbiology
https://www.readbyqxmd.com/read/29776607/differentiation-of-equine-bone-marrow-derived-mesenchymal-stem-cells-increases-the-expression-of-immunogenic-genes
#3
Laura Barrachina, Ana Rosa Remacha, Antonio Romero, Pilar Zaragoza, Francisco José Vázquez, Clementina Rodellar
Mesenchymal stem cells (MSCs) are a promising treatment for equine musculoskeletal injuries because of their ability to regulate the inflammation and to differentiate into other cell types. Since interest in allogeneic therapy is rising, concerns about MSC immunogenicity need to be addressed. Differentiated MSCs from several species increase their expression of immunogenic molecules and induce alloresponses, but equine MSC immunogenic profile after differentiation has not been reported. Therefore, the aim of this study was to assess the gene expression of immunogenic markers in tri-lineage differentiated equine bone marrow derived MSCs (eBM-MSCs)...
June 2018: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/29776088/how-nonuniform-contact-profiles-of-t-cell-receptors-modulate-thymic-selection-outcomes
#4
Hanrong Chen, Arup K Chakraborty, Mehran Kardar
T cell receptors (TCRs) bind foreign or self-peptides attached to major histocompatibility complex (MHC) molecules, and the strength of this interaction determines T cell activation. Optimizing the ability of T cells to recognize a diversity of foreign peptides yet be tolerant of self-peptides is crucial for the adaptive immune system to properly function. This is achieved by selection of T cells in the thymus, where immature T cells expressing unique, stochastically generated TCRs interact with a large number of self-peptide-MHC; if a TCR does not bind strongly enough to any self-peptide-MHC, or too strongly with at least one self-peptide-MHC, the T cell dies...
March 2018: Physical Review. E
https://www.readbyqxmd.com/read/29772011/induction-of-influenza-specific-local-cd8-t-cells-in-the-respiratory-tract-after-aerosol-delivery-of-vaccine-antigen-or-virus-in-the-babraham-inbred-pig
#5
Katie Tungatt, Garry Dolton, Sophie B Morgan, Meriem Attaf, Anna Fuller, Thomas Whalley, Johanneke D Hemmink, Emily Porter, Barbara Szomolay, Maria Montoya, John A Hammond, John J Miles, David K Cole, Alain Townsend, Mick Bailey, Pierre J Rizkallah, Bryan Charleston, Elma Tchilian, Andrew K Sewell
There is increasing evidence that induction of local immune responses is a key component of effective vaccines. For respiratory pathogens, for example tuberculosis and influenza, aerosol delivery is being actively explored as a method to administer vaccine antigens. Current animal models used to study respiratory pathogens suffer from anatomical disparity with humans. The pig is a natural and important host of influenza viruses and is physiologically more comparable to humans than other animal models in terms of size, respiratory tract biology and volume...
May 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29771935/cell-iron-status-influences-macrophage-polarization
#6
Rafiou Agoro, Meriem Taleb, Valerie F J Quesniaux, Catherine Mura
Macrophages play crucial roles in innate immune response and in the priming of adaptive immunity, and are characterized by their phenotypic heterogeneity and plasticity. Reprogramming intracellular metabolism in response to microenvironmental signals is required for M1/M2 macrophage polarization and function. Here we assessed the influence of iron on the polarization of the immune response in vivo and in vitro. Iron-enriched diet increased M2 marker Arg1 and Ym1 expression in liver and peritoneal macrophages, while iron deficiency decreased Arg1 expression...
2018: PloS One
https://www.readbyqxmd.com/read/29769317/lysophospholipids-induce-innate-immune-transdifferentiation-of-endothelial-cells-resulting-in-prolonged-endothelial-activation
#7
Xinyuan Li, Luqiao Wang, Pu Fang, Yu Sun, Xiaohua Jiang, Hong Wang, Xiao-Feng Yang
Innate immune cells express danger-associated molecular pattern (DAMP) receptors, T-cell co-stimulation/co-inhibition receptors, and the major histocompatibility complex II (MHC-II). We have recently proposed that endothelial cells can serve as innate immune cells, but the molecular mechanisms involved still await discovery. Here, we investigated whether human aortic endothelial cells (HAECs) could be transdifferentiated into innate immune cells by exposing them to hyperlipidemia-upregulated DAMP molecules, i...
May 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29766368/systemic-contact-dermatitis
#8
REVIEW
Marcella Aquino, Greg Rosner
Systemic contact dermatitis (SCD) traditionally refers to a skin condition where an individual who is cutaneously sensitized to an allergen will subsequently react to that same allergen or a cross reacting allergen via a different route. It occurs to allergens including metals, medications, and foods. The exact pathophysiology underlying this disease remains unknown, although it appears to be mediated by type 4 hypersensitivity reactions and possibly type 3 hypersensitivity reactions. The p-I concept (pharmacologic interaction with immunoreceptors) hypothesized that drugs are able to bind directly to a T cell receptor without first being presented by MHC (major histocompatibility complex) molecules and without prior metabolism, which would help explain why SCD can be seen on first exposure to medications...
May 15, 2018: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/29765374/mica-129-dimorphism-and-soluble-mica-are-associated-with-the-progression-of-multiple-myeloma
#9
Alessandra Zingoni, Elisabetta Vulpis, Francesca Cecere, Maria G Amendola, Daniel Fuerst, Taron Saribekyan, Adnane Achour, Tatyana Sandalova, Ilaria Nardone, Agnese Peri, Alessandra Soriani, Cinzia Fionda, Elena Mariggiò, Maria T Petrucci, Maria R Ricciardi, Joannis Mytilineos, Marco Cippitelli, Cristina Cerboni, Angela Santoni
Natural killer (NK) cells are immune innate effectors playing a pivotal role in the immunosurveillance of multiple myeloma (MM) since they are able to directly recognize and kill MM cells. In this regard, among activating receptors expressed by NK cells, NKG2D represents an important receptor for the recognition of MM cells, being its ligands expressed by tumor cells, and being able to trigger NK cell cytotoxicity. The MHC class I-related molecule A (MICA) is one of the NKG2D ligands; it is encoded by highly polymorphic genes and exists as membrane-bound and soluble isoforms...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29763778/mage-a-antigens-as-targets-for-cancer-immunotherapy
#10
REVIEW
Erik Schooten, Alessia Di Maggio, Paul M P van Bergen En Henegouwen, Marta M Kijanka
Targeted anti-cancer therapies aim at reducing side effects while retaining their anti-cancer efficacy. Immunotherapies e.g. monoclonal antibodies, adoptive T cell therapy and cancer vaccines are used to combat cancer, but the number of available cancer specific targets is limited and new approaches are needed to generate more effective and patient tailored treatments. Unique cancer intracellular epitopes can be presented on the cell surface by MHC class I molecules, which can function as epitopes for targeted therapies...
April 26, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29761100/moving-the-cellular-peptidome-by-transporters
#11
REVIEW
Rupert Abele, Robert Tampé
Living matter is defined by metastability, implying a tightly balanced synthesis and turnover of cellular components. The first step of eukaryotic protein degradation via the ubiquitin-proteasome system (UPS) leads to peptides, which are subsequently degraded to single amino acids by an armada of proteases. A small fraction of peptides, however, escapes further cytosolic destruction and is transported by ATP-binding cassette (ABC) transporters into the endoplasmic reticulum (ER) and lysosomes. The ER-resident heterodimeric transporter associated with antigen processing (TAP) is a crucial component in adaptive immunity for the transport and loading of peptides onto major histocompatibility complex class I (MHC I) molecules...
2018: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29760718/multiplexed-nanopore-sequencing-of-hla-b-locus-in-m%C3%A4-ori-and-pacific-island-samples
#12
Kim N T Ton, Simone L Cree, Sabine J Gronert-Sum, Tony R Merriman, Lisa K Stamp, Martin A Kennedy
The human leukocyte antigen (HLA) system encodes the human major histocompatibility complex (MHC). HLA-B is the most polymorphic gene in the MHC class I region and many HLA-B alleles have been associated with adverse drug reactions (ADRs) and disease susceptibility. The frequency of such HLA-B alleles varies by ethnicity, and therefore it is important to understand the prevalence of such alleles in different population groups. Research into HLA involvement in ADRs would be facilitated by improved methods for genotyping key HLA-B alleles...
2018: Frontiers in Genetics
https://www.readbyqxmd.com/read/29756405/duplicated-major-histocompatibility-complex-class-ii-genes-in-the-tongue-sole-cynoglossus-semilaevis
#13
C Li, J Jiang, Q Zhang, X Wang
The major histocompatibility complex (MHC) molecule plays an important role in the vertebrate immune system. However, we have a limited understanding of the MHC genomic structure in teleosts. Using gene cloning and family analysis, we isolate the MHC class II genes in the tongue sole (Cynoglossus semilaevis) and find that both class II A and class II B genes are duplicated (named Cyse-DAA and Cyse-DBA, Cyse-DAB and Cyse-DBB, respectively). The class II A genes consist of four exons with a highly conserved genomic structure, but each gene has unique and defining exon 2 and intron 2 sequences...
May 13, 2018: International Journal of Immunogenetics
https://www.readbyqxmd.com/read/29755461/efficient-uptake-of-recombinant-lipidated-survivin-by-antigen-presenting-cells-initiates-antigen-cross-presentation-and-antitumor-immunity
#14
Chen-Yi Chiang, Yi-Jyun Chen, Chiao-Chieh Wu, Shih-Jen Liu, Chih-Hsiang Leng, Hsin-Wei Chen
Survivin is overexpressed in various types of human cancer, but rarely expressed in terminally differentiated adult tissues. Thus, survivin is a potential target antigen for a cancer vaccine. However, self-tumor-associated antigens are not highly immunogenic. Bacteria-derived lipoproteins can activate antigen-presenting cells through their toll-like receptors to enhance immune responses. In this context, lipidated survivin is an attractive candidate for cancer immunotherapy. In the present study, recombinant lipidated human survivin (LSur) was prepared from an Escherichia coli -based system...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29752262/cd4-t-cell-mediated-rejection-of-mhc-class-ii-positive-tumor-cells-is-dependent-on-antigen-secretion-and-indirect-presentation-on-host-apcs
#15
Ole Audun Werner Haabeth, Marte Fauskanger, Melanie Manzke, Katrin U Lundin, Alexandre Corthay, Bjarne Bogen, Anders Aune Tveita
Tumor-specific CD4+ T cells have been shown to mediate efficient anti-tumor immune responses against cancer. Such responses can occur through direct binding to MHC class II (MHC II)-expressing tumor cells or indirectly via activation of professional antigen-presenting cells (APC) that take up and present the tumor antigen. We have previously shown that CD4+ T cells reactive against an epitope within the Ig light chain variable region of a murine B cell lymphoma can reject established tumors. Given the presence of MHC II molecules at the surface of lymphoma cells, we investigated whether MHC II-restricted antigen presentation on tumor cells alone was required for rejection...
May 11, 2018: Cancer Research
https://www.readbyqxmd.com/read/29751114/very-low-numbers-of-cd4-foxp3-tregs-expanded-in-donors-via-tl1a-ig-and-low-dose-il-2-exhibit-a-distinct-activation-functional-profile-and-suppress-gvhd-in-a-pre-clinical-model
#16
Sabrina Copsel, Dietlinde Wolf, Brandon Kale, Henry Barreras, Casey O Lightbourn, Cameron S Bader, W Alperstein, Norman H Altman, Krishna V Komanduri, Robert B Levy
Regulatory T cells (Tregs) are essential for the maintenance of tolerance and immune homeostasis. In allogeneic hematopoietic stem cell transplantation (aHSCT), transfer of appropriate Treg numbers is a promising therapy for the prevention of graft-versus-host disease (GVHD). We have recently reported a novel approach which induces the marked expansion and selective activation of Tregs in vivo by targeting TNF receptor superfamily 25 (TNFRSF25) and CD25. A potential advance to promote clinical application of Treg cells to ameliorate GVHD and other disorders would be the generation of more potent Treg populations...
May 8, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29743369/intrastructural-help-harnessing-t-helper-cells-induced-by-licensed-vaccines-for-improvement-of-hiv-env-antibody-responses-to-virus-like-particle-vaccines
#17
Hassan Elsayed, Ghulam Nabi, William J McKinstry, Keith K Khoo, Johnson Mak, Andres M Salazar, Matthias Tenbusch, Vladimir Temchura, Klaus Überla
Induction of persistent antibody responses by vaccination is generally thought to depend on efficient help by T follicular helper cells. Since the T helper cell response to HIV Env may not be optimal, we explored the possibility to improve the HIV Env antibody response to virus-like particle (VLP) vaccines by recruiting T helper cells induced by a commonly-used licensed vaccines to provide help for Env-specific B cells. B cells specific for the surface protein of a VLP can internalize the entire VLP and thus present peptides derived from the surface and core proteins on their MHC-II molecules...
May 9, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29738961/lipids-hide-or-step-aside-for-cd1-autoreactive-t-cell-receptors
#18
REVIEW
Rachel N Cotton, Adam Shahine, Jamie Rossjohn, D Branch Moody
Peptide and lipid antigens are presented to T cells when bound to MHC or CD1 proteins, respectively. The general paradigm of T cell antigen recognition is that T cell receptors (TCRs) co-recognize an epitope comprised of the antigen and antigen presenting molecule. Here we review the latest studies in which T cells operate outside the co-recognition paradigm: TCRs can broadly contact CD1 itself, but not the carried lipid. The essential structural feature in these new mechanisms is a large 'antigen free' zone on the outer surface of certain antigen presenting molecules...
May 4, 2018: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29730801/challenges-and-prospects-of-chimeric-antigen-receptor-t-cell-therapy-in-solid-tumors
#19
REVIEW
Vishal Jindal, Ena Arora, Sorab Gupta
Chimeric antigen receptor (CAR) T cell therapy is a novel and innovative immunotherapy. CAR-T cells are genetically engineered T cells, carrying MHC independent specific antigen receptor and co-stimulatory molecule which can activate an immune response to a cancer specific antigen. This therapy showed great results in hematological malignancies but were unable to prove their worth in solid tumors. Likely reasons for their failure are lack of antigens, poor trafficking, and hostile tumor microenvironment. Excessive amount of research is going on to improve the efficacy of CAR T cell therapy in solid tumors...
May 5, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29724463/analysis-of-epitope-based-vaccine-candidates-against-the-e-antigen-of-the-hepatitis-b-virus-based-on-the-b-genotype-sequence-an-in-silico-and-in-vitro-approach
#20
Juzeng Zheng, Zhanfan Ou, Xianfan Lin, Lingling Wang, Yang Liu, Sisi Jin, Jinming Wu
Chronic hepatitis B virus infection is a worldwide health problem with no current effective strategy to achieve a cure. The Hepatitis B virus (HBV) E antigen (HBeAg) has a negative effect on the immune system and a therapeutic vaccine is a promising strategy in order to treat chronic virus infection. In this study, we analyzed and identified the MHC-I, MHC-II and B cell epitopes of the HBeAg based on a B genotype sequence of HBV using a bioinformatic approach and in vitro experiments. The computational approach provided us with four epitopes (LLWFHISCL, YLVSFGVWI, MQLFHLCLI, TVLEYLVSF) of the specific MHC-I allele HLA-A0201 that conformed to all criteria...
April 30, 2018: Cellular Immunology
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