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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/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
#2
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/29765374/mica-129-dimorphism-and-soluble-mica-are-associated-with-the-progression-of-multiple-myeloma
#3
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/29764836/subcellular-localization-of-antigen-dictates-delivery-of-cd4-t-cell-help-for-the-ctl-response-upon-therapeutic-dna-vaccination-into-the-skin
#4
Nikolina Bąbała, Astrid Bovens, Evert de Vries, Victoria Iglesias-Guimarais, Tomasz Ahrends, Matthew F Krummel, Jannie Borst, Adriaan D Bins
In a mouse model of therapeutic DNA vaccination, we studied how the subcellular localization of vaccine protein impacts antigen delivery to professional antigen presenting cells (pAPCs) and efficiency of CTL priming. Cytosolic, membrane-bound, nuclear, and secretory versions of ZsGreen fluorescent protein, conjugated to MHC class I and -II ovalbumin (OVA) epitopes were expressed in keratinocytes by DNA vaccination into the skin. ZsGreen-OVA versions reached B cells in the skin-draining lymph node (dLN) that proved irrelevant for CTL priming...
May 15, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29763778/mage-a-antigens-as-targets-for-cancer-immunotherapy
#5
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
#6
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
#7
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/29752315/formation-of-immune-complexes-with-a-tetanus-derived-b-cell-epitope-boosts-human-t-cell-responses-to-covalently-linked-peptides-in-an-ex-vivo-blood-loop-system
#8
Erika A K Fletcher, Wendy van Maren, Robert Cordfunke, Jasper Dinkelaar, Jeroen D C Codee, Gijs van der Marel, Cornelis J M Melief, Ferry Ossendorp, Jan Wouter Drijfhout, Sara M Mangsbo
Enhancing T cell responses against both viral and tumor Ags requires efficient costimulation and directed delivery of peptide Ags into APCs. Long peptide vaccines are considered favorable vaccine moieties from a clinical perspective, as they can harbor more than one immunogenic epitope enabling treatment of a broader target population. In addition, longer peptides are not extracellularly loaded on MHC class I; rather, they require intracellular processing and will thereby be presented to T cells mainly by professional APCs, thereby avoiding the risk of tolerance induction...
May 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29743316/hla-f-on-hla-null-721-221-cells-activates-primary-nk-cells-expressing-the-activating-killer-ig-like-receptor-kir3ds1
#9
Zahra Kiani, Franck P Dupuy, Julie Bruneau, Bertrand Lebouché, Cindy X Zhang, Elise Jackson, Irene Lisovsky, Sandrina da Fonseca, Daniel E Geraghty, Nicole F Bernard
NK cells elicit important responses against transformed and virally infected cells. Carriage of the gene encoding the activating killer Ig-like receptor KIR3DS1 is associated with slower time to AIDS and protection from HIV infection. Recently, open conformers of the nonclassical MHC class Ib Ag HLA-F were identified as KIR3DS1 ligands. In this study, we investigated whether the interaction of KIR3DS1 on primary NK cells with HLA-F on the HLA-null cell line 721.221 (221) stimulated KIR3DS1+ NK cells. We used a panel of Abs to detect KIR3DS1+ CD56dim NK cells that coexpressed the inhibitory NK cell receptors KIR2DL1/L2/L3, 3DL2, NKG2A, and ILT2; the activating NK cell receptors KIR2DS1/S2/S3/S5; and CCL4, IFN-γ, and CD107a functions...
May 9, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29741393/molecular-docking-of-immunogenic-peptide-of-toxoplasma-gondii-and-encapsulation-with-polymer-as-vaccine-candidate
#10
Rabia Cakir-Koc, Yasemin Budama-Kilinc, Yagmur Kokcu, Serda Kecel-Gunduz
Toxoplasma gondii is one of the most widely spread parasitic organisms in the world. T. gondii causes primary, chronic infection and mortality. Major surface antigen 1 is the most abundant tachyzoite surface protein and highly conserved between species and causes strong humoural response. Some studies showed that the peptide sequence of surface antigen has immunity. Therefore, tachyzoite surface antigenic peptide sequence is one of the good candidates for vaccine development. However, conformational information and delivery systems are very important parameters for vaccine development...
May 9, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29739853/mycobacterium-tuberculosis-ppe60-antigen-drives-th1-th17-responses-via-toll-like-receptor-2-dependent-maturation-of-dendritic-cells
#11
Haibo Su, Zhen Zhang, Zijian Liu, Baozhou Peng, Cong Kong, Honghai Wang, Zhi Zhang, Ying Xu
Targeting of Mycobacterium tuberculosis (MTB) PE/PPE antigens that induce type 1 helper T cell (Th1) and Th17 responses represents a crucial strategy for the development of tuberculosis (TB) vaccines. However, only few PE/PPE antigens induce these responses. Here, we sought to determine how the cell wall-associated antigen PPE60 (Rv3478) activates dendritic cell (DC) maturation and T-cell differentiation. We observed that PPE60 induces DC maturation by augmenting the protein expression of cluster of differentiation 80 (CD80) and CD86, and major histocompatibility complex (MHC) class I and MHC class II on the cell surface...
May 8, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29738610/lmp2-immunoproteasome-promotes-lymphocyte-survival-by-degrading-apoptotic-bh3-only-proteins
#12
Damien Zanker, Kenneth Pang, Sara Oveissi, Chunni Lu, Pierre Faou, Cameron Nowell, George Williams Mbogo, Sebastian Carotta, Cathy Quillici, Guna Karupiah, Margaret Hibbs, Stephen L Nutt, Paul Neeson, Hamsa Puthalakath, Weisan Chen
The role of the immunoproteasome is perceived as confined to adaptive immune responses given its ability to produce peptides ideal for MHC Class-I binding. Here, we demonstrate that the immunoproteasome subunit, LMP2, has functions beyond its immunomodulatory role. Using LMP2-deficient mice, we demonstrate that LMP2 is crucial for lymphocyte development and survival in the periphery. Moreover, LMP2-deficient lymphocytes show impaired degradation of key BH3-only proteins, resulting in elevated levels of pro-apoptotic BIM and increased cell death...
May 8, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29738531/the-secreted-theileria-annulata-ta9-protein-contributes-to-activation-of-the-ap-1-transcription-factor
#13
Ahmet Hakan Unlu, Shahin Tajeri, Huseyin Bilgin Bilgic, Hasan Eren, Tulin Karagenc, Gordon Langsley
Theileria annulata is an obligate intracellular protozoan parasite of the phylum Apicomplexa. Theileria sporozoites invade bovine leukocytes and develop into a multinucleate syncytial macroschizont that causes uncontrolled proliferation and dissemination of infected and transformed leukocytes. Activator protein 1 (AP-1) is a transcription factor driving expression of genes involved in proliferation and dissemination and is therefore a key player in Theileria-induced leukocytes transformation. Ta9 possesses a signal peptide allowing it to be secreted into the infected leukocyte cytosol and be presented to CD8 T cells in the context of MHC class I...
2018: PloS One
https://www.readbyqxmd.com/read/29737898/exposure-to-low-dose-bisphenol-a-during-the-juvenile-period-of-development-disrupts-the-immune-system-and-aggravates-allergic-airway-inflammation-in-mice
#14
Eiko Koike, Rie Yanagisawa, Tin-Tin Win-Shwe, Hirohisa Takano
Bisphenol A (BPA) is used in the production of polycarbonate plastics and epoxy resins and found in many consumer products. Previous studies have reported that perinatal exposure to BPA through the oral route promotes the development of allergic airway inflammation. We investigated the effects of exposure to low-dose BPA during the juvenile period of development on allergic airway inflammation. Six-week-old male C3H/HeJ mice were intratracheally administered ovalbumin (OVA, 1 μg) every 2 weeks and/or BPA (0, 0...
January 2018: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/29728507/previously-hidden-dynamics-at-the-tcr-peptide-mhc-interface-revealed
#15
James Fodor, Blake T Riley, Natalie A Borg, Ashley M Buckle
A structural characterization of the interaction between αβ TCRs and cognate peptide-MHC (pMHC) is central to understanding adaptive T cell-mediated immunity. X-ray crystallography, although the source of much structural data, traditionally provides only a static snapshot of the protein. Given the emerging evidence for the important role of conformational dynamics in protein function, we interrogated 309 crystallographic structures of pMHC complexes using ensemble refinement, a technique that can extract dynamic information from the x-ray data...
May 4, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29723118/protective-effects-of-interferon-tau-against-lipopolysaccharide-induced-embryo-implantation-failure-in-pregnant-mice
#16
Kangfeng Jiang, Jing Yang, Yu Chen, Shuai Guo, Gan Zhao, Haichong Wu, Ganzhen Deng
Interferon-tau (IFN-τ), a novel type I interferon, is produced by trophoblast cells in ruminants. Previous studies have confirmed that IFN-τ could induce immunological tolerance in humans and other species. However, there are few reports on whether IFN-τ has a protective effect on embryo implantation failure caused by excessive inflammation at the maternal-fetal interface. In our study, a mouse model of lipopolysaccharide (LPS)-induced implantation failure was successfully established, and we investigated the protective effects of IFN-τ...
May 3, 2018: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/29721164/novel-therapeutic-features-of-disulfiram-against-hepatocellular-carcinoma-cells-with-inhibitory-effects-on-a-disintegrin-and-metalloproteinase-10
#17
Kaku Goto, Jun Arai, Anthony Stephanou, Naoya Kato
Our previous genome-wide association study identified the anti-tumor ligand MHC class I polypeptide-related sequence A ( MICA ) as a susceptibility gene for hepatitis C virus-induced hepatocellular carcinoma (HCC). We subsequently proved that pharmacological restoration of membrane-bound MICA in HCC cells boosted natural killer cell-mediated anti-cancer effects, confirming that a MICA sheddase, a disintegrin and metalloproteinase 10 (ADAM10), is a therapeutic target. We here searched for approved drugs with inhibitory effects on ADAM10 in vitro , and the anti-alcoholism agent, disulfiram, was identified...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29721030/meta-populational-demes-constitute-a-reservoir-for-large-mhc-allele-diversity-in-wild-house-mice-mus-musculus
#18
Miriam Linnenbrink, Meike Teschke, Inka Montero, Marie Vallier, Diethard Tautz
Background: The MHC class I and II loci mediate the adaptive immune response and belong to the most polymorphic loci in vertebrate genomes. In fact, the number of different alleles in a given species is often so large that it remains a challenge to provide an evolutionary model that can fully account for this. Results: We provide here a general survey of MHC allele numbers in house mouse populations and two sub-species ( M. m. domesticus and M. m. musculus ) for H2 class I D and K, as well as class II A and E loci...
2018: Frontiers in Zoology
https://www.readbyqxmd.com/read/29720698/exploring-leptospiral-proteomes-to-identify-potential-candidates-for-vaccine-design-against-leptospirosis-using-an-immunoinformatics-approach
#19
Kumari Snehkant Lata, Swapnil Kumar, Vibhisha Vaghasia, Priyanka Sharma, Shivarudrappa B Bhairappanvar, Subhash Soni, Jayashankar Das
Leptospirosis is the most widespread zoonotic disease, estimated to cause severe infection in more than one million people each year, particularly in developing countries of tropical areas. Several factors such as variable and nonspecific clinical manifestation, existence of large number of serovars and asymptomatic hosts spreading infection, poor sanitation and lack of an effective vaccine make prophylaxis difficult. Consequently, there is an urgent need to develop an effective vaccine to halt its spread all over the world...
May 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29719275/endocytosis-regulation-by-autophagy-proteins-in-mhc-restricted-antigen-presentation
#20
REVIEW
Christian W Keller, Monica Loi, Laure-Anne Ligeon, Monique Gannagé, Jan D Lünemann, Christian Münz
The macroautophagy machinery supports membrane remodeling and fusion events that lead to the engulfment of cytoplasmic constituents in autophagosomes and their degradation in lysosomes. The capacity of this machinery to regulate membrane adaptors and influence vesicle fusion with lysosomes seems to be used not only for autophagosomes, but also for endosomes. We summarize recent evidence that two aspects of endocytosis are regulated by parts of the macroautophagy machinery. These are recruitment of adaptors for the internalization of surface receptors and the fusion of phagosomes with lysosomes...
April 29, 2018: Current Opinion in Immunology
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