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https://www.readbyqxmd.com/read/28218747/mhc-i-peptides-get-out-of-the-groove-and-enable-a-novel-mechanism-of-hiv-1-escape
#1
Phillip Pymm, Patricia T Illing, Sri H Ramarathinam, Geraldine M O'Connor, Victoria A Hughes, Corinne Hitchen, David A Price, Bosco K Ho, Daniel W McVicar, Andrew G Brooks, Anthony W Purcell, Jamie Rossjohn, Julian P Vivian
Major histocompatibility complex class I (MHC-I) molecules play a crucial role in immunity by capturing peptides for presentation to T cells and natural killer (NK) cells. The peptide termini are tethered within the MHC-I antigen-binding groove, but it is unknown whether other presentation modes occur. Here we show that 20% of the HLA-B*57:01 peptide repertoire comprises N-terminally extended sets characterized by a common motif at position 1 (P1) to P2. Structures of HLA-B*57:01 presenting N-terminally extended peptides, including the immunodominant HIV-1 Gag epitope TW10 (TSTLQEQIGW), showed that the N terminus protrudes from the peptide-binding groove...
February 20, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28218671/human-scfvs-that-counteract-bioactivities-of-staphylococcus-aureus-tsst-1
#2
Thunchanok Rukkawattanakul, Nitat Sookrung, Watee Seesuay, Nattawat Onlamoon, Pornphan Diraphat, Wanpen Chaicumpa, Nitaya Indrawattana
Some Staphylococcus aureus isolates produced toxic shock syndrome toxin-1 (TSST-1) which is a pyrogenic toxin superantigen (PTSAg). The toxin activates a large fraction of peripheral blood T lymphocytes causing the cells to proliferate and release massive amounts of pro-inflammatory cytokines leading to a life-threatening multisystem disorder: toxic shock syndrome (TSS). PTSAg-mediated-T cell stimulation circumvents the conventional antigenic peptide presentation to T cell receptor (TCR) by the antigen-presenting cell (APC)...
February 17, 2017: Toxins
https://www.readbyqxmd.com/read/28215281/emerging-major-histocompatibility-complex-class-i-related-functions-of-nlrc5
#3
S T Chelbi, A T Dang, G Guarda
Recent evidence demonstrates a key role for the nucleotide-binding oligomerization domain-like receptor (NLR) family member NLRC5 (NLR family, CARD domain containing protein 5) in the transcriptional regulation of major histocompatibility complex (MHC) class I and related genes. Detailed information on NLRC5 target genes in various cell types and conditions is emerging. Thanks to its analogy to CIITA (class II major MHC transactivator), a NLR family member known for over 20 years to be the master regulator of MHC class II gene transcription, also the molecular mechanisms underlying NLRC5 function are being rapidly unraveled...
2017: Advances in Immunology
https://www.readbyqxmd.com/read/28212574/the-combined-action-of-mast-cell-chymase-tryptase-and-carboxypeptidase-a3-protects-against-melanoma-colonization-of-the-lung
#4
Mirjana Grujic, Aida Paivandy, Ann-Marie Gustafson, Allan R Thomsen, Helena Öhrvik, Gunnar Pejler
Mast cell secretory granules are densely packed with various bioactive mediators including proteases of chymase, tryptase and CPA3 type. Previous studies have indicated that mast cells can affect the outcome of melanoma but the contribution of the mast cell granule proteases to such effects has not been clear. Here we addressed this issue by assessing mice lacking either the chymase Mcpt4, the tryptase Mcpt6 or carboxypeptidase A3 (Cpa3), as well as mice simultaneously lacking all three proteases, in a model of melanoma dissemination from blood to the lung...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28210263/a-paradigm-shift-on-the-question-of-b-cells-in-transplantation-recent-insights-on-regulating-the-alloresponse
#5
REVIEW
Daniel J Firl, Gilles Benichou, James I Kim, Heidi Yeh
B lymphocytes contribute to acute and chronic allograft rejection through their production of donor-specific antibodies (DSAs). In addition, B cells present allopeptides bound to self-MHC class II molecules and provide costimulation signals to T cells, which are essential to their activation and differentiation into memory T cells. On the other hand, both in laboratory rodents and patients, the concept of effector T cell regulation by B cells is gaining traction in the field of transplantation. Specifically, clinical trials using anti-CD20 monoclonal antibodies to deplete B cells and reverse DSA had a deleterious effect on rates of acute cellular rejection; a peculiar finding that calls into question a central paradigm in transplantation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28208600/invariant-chain-complexes-and-clusters-as-platforms-for-mif-signaling
#6
REVIEW
Robert Lindner
Invariant chain (Ii/CD74) has been identified as a surface receptor for migration inhibitory factor (MIF). Most cells that express Ii also synthesize major histocompatibility complex class II (MHC II) molecules, which depend on Ii as a chaperone and a targeting factor. The assembly of nonameric complexes consisting of one Ii trimer and three MHC II molecules (each of which is a heterodimer) has been regarded as a prerequisite for efficient delivery to the cell surface. Due to rapid endocytosis, however, only low levels of Ii-MHC II complexes are displayed on the cell surface of professional antigen presenting cells and very little free Ii trimers...
February 10, 2017: Cells
https://www.readbyqxmd.com/read/28203232/cationic-net-charge-and-counter-ion-type-as-antimicrobial-activity-determinant-factors-of-short-lipopeptides
#7
Katarzyna E Greber, Malgorzata Dawgul, Wojciech Kamysz, Wieslaw Sawicki
To get a better insight into the antimicrobial potency of short cationic lipopeptides, 35 new entities were synthesized using solid phase peptide strategy. All newly obtained lipopeptides were designed to be positively charged from +1 to +4. This was achieved by introducing basic amino acid - lysine - into the lipopeptide structure and had a hydrophobic fatty acid chain attached. Lipopeptides were subjected to microbiological tests using reference strains of Gram-negative bacteria: Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, Pseudomonas aeruginosa, Gram-positive bacteria: Staphylococcus aureus, Staphylococcus epidermidis, Bacillus subtilis, Enterococcus faecalis, and fungi: Candida albicans, Candida tropicalis, Aspergillus brasiliensis...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28197373/systemic-activation-of-antigen-presenting-cells-via-rna-loaded-nanoparticles
#8
Elias J Sayour, Gabriel De Leon, Christina Pham, Adam Grippin, Hanna Kemeny, Joshua Chua, Jianping Huang, John H Sampson, Luis Sanchez-Perez, Catherine Flores, Duane A Mitchell
While RNA-pulsed dendritic cell (DC) vaccines have shown promise, the advancement of cellular therapeutics is fraught with developmental challenges. To circumvent the challenges of cellular immunotherapeutics, we developed clinically translatable nanoliposomes that can be combined with tumor-derived RNA to generate personalized tumor RNA-nanoparticles (NPs) with considerable scale-up capacity. RNA-NPs bypass MHC restriction, are amenable to central distribution, and can provide near immediate immune induction...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28188227/the-hla-b27-peptidome-in-vivo-in-spondyloarthritis-susceptible-hla-b27-transgenic-rats-and-the-effect-of-erap1-deletion
#9
Eilon Barnea, Dganit Melamed Kadosh, Yael Haimovich, Nimman Satumtira, Martha L Dorris, Mylinh T Nguyen, Robert E Hammer, Tri M Tran, Robert A Colbert, Joel D Taurog, Arie Admon
HLA-B27 is a class I major histocompatibility (MHC-I) allele that confers susceptibility to the rheumatic disease ankylosing spondylitis (AS) by an unknown mechanism. ERAP1 is an aminopeptidase that trims peptides in the endoplasmic reticulum for binding to MHC-I molecules. ERAP1 shows genetic epistasis with HLA-B27 in conferring susceptibility to AS. Male HLA-B27 transgenic rats develop arthritis and serve as an animal model of AS, whereas female B27 transgenic rats remain healthy. We used large-scale quantitative mass-spectrometry to identify over 15,000 unique HLA-B27 peptide ligands, isolated after immunoaffinity purification of the B27 molecules from the spleens of HLA-B27 transgenic rats...
February 10, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28179460/vamp-7-dependent-secretion-at-the-immune-synapse-regulates-antigen-extraction-and-presentation-in-b-lymphocytes
#10
Dorian Obino, Jheimmy Diaz, Juan José Sáez, Jorge Ibañez-Vega, Pablo J Sáez, Martina Alamo, Danielle Lankar, Maria-Isabel Yuseff
Recognition of surface-tethered antigens (Ag) by B cells leads to the formation of an immune synapse that promotes Ag uptake for presentation onto MHC-II molecules. Extraction of immobilized antigens at the immune synapse of B cells relies on the local secretion of lysosomes, which are recruited to the antigen contact site by polarization of their microtubule network. Although conserved polarity proteins have been implicated in coordinating cytoskeleton remodeling with lysosome trafficking, the cellular machinery associated with lysosomal vesicles that regulates their docking and secretion at the synaptic interface has not been defined...
February 8, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28179428/breaking-confinement-unconventional-peptide-presentation-by-major-histocompatibility-mhc-class-i-allele-hla-a-02-01
#11
Soumya G Remesh, Massimo Andreatta, Ge Ying, Thomas Kaever, Morten Nielsen, Curtis McMurtrey, William Hildebrand, Bjoern Peters, Dirk M Zajonc
Peptide antigen-presentation by Major Histocompatibility Class (MHC) I proteins initiates CD8+ T cell mediated immunity against pathogens and cancers. MHC I molecules typically bind peptides with nine amino acids in length with both ends tucked inside the major A and F binding pocket. It has been known for a while that longer peptides can also bind by either bulging out of the groove in the middle of the peptide or by binding in a zig-zag fashion inside the groove. In a recent study, we identified an alternative binding conformation of naturally occurring peptides from Toxoplasma gondii bound by HLA-A*02:01...
February 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28169322/collagen-scaffold-microenvironments-modulate-cell-lineage-commitment-for-differentiation-of-bone-marrow-cells-into-regulatory-dendritic-cells
#12
Yongxiang Fang, Bin Wang, Yannan Zhao, Zhifeng Xiao, Jing Li, Yi Cui, Sufang Han, Jianshu Wei, Bing Chen, Jin Han, Qingyuan Meng, Xianglin Hou, Jianxun Luo, Jianwu Dai, Zhizhong Jing
The microenvironment plays a pivotal role for cell survival and functional regulation, and directs the cell fate determination. The biological functions of DCs have been extensively investigated to date. However, the influences of the microenvironment on the differentiation of bone marrow cells (BMCs) into dendritic cells (DCs) are not well defined. Here, we established a 3D collagen scaffold microenvironment to investigate whether such 3D collagen scaffolds could provide a favourable niche for BMCs to differentiate into specialised DCs...
February 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28168174/sh2-domain-containing-adaptor-protein-b-expressed-in-dendritic-cells-is-involved-in-t-cell-homeostasis-by-regulating-dendritic-cell-mediated-th2-immunity
#13
Md Selim Ahmed, Myeong-Ho Kang, Ezra Lee, Yujin Park, Yideul Jeong, Yong-Soo Bae
PURPOSE: The Src homology 2 domain-containing adaptor protein B (SHB) is widely expressed in immune cells and acts as an important regulator for hematopoietic cell function. SHB silencing induces Th2 immunity in mice. SHB is also involved in T-cell homeostasis in vivo. However, SHB has not yet been studied and addressed in association with dendritic cells (DCs). MATERIALS AND METHODS: The effects of SHB expression on the immunogenicity of DCs were assessed by Shb gene silencing in mouse bone marrow-derived DCs (BMDCs)...
January 2017: Clinical and Experimental Vaccine Research
https://www.readbyqxmd.com/read/28166217/drugs-and-drug-like-molecules-can-modulate-the-function-of-mucosal-associated-invariant-t-cells
#14
Andrew N Keller, Sidonia B G Eckle, Weijun Xu, Ligong Liu, Victoria A Hughes, Jeffrey Y W Mak, Bronwyn S Meehan, Troi Pediongco, Richard W Birkinshaw, Zhenjun Chen, Huimeng Wang, Criselle D'Souza, Lars Kjer-Nielsen, Nicholas A Gherardin, Dale I Godfrey, Lyudmila Kostenko, Alexandra J Corbett, Anthony W Purcell, David P Fairlie, James McCluskey, Jamie Rossjohn
The major-histocompatibility-complex-(MHC)-class-I-related molecule MR1 can present activating and non-activating vitamin-B-based ligands to mucosal-associated invariant T cells (MAIT cells). Whether MR1 binds other ligands is unknown. Here we identified a range of small organic molecules, drugs, drug metabolites and drug-like molecules, including salicylates and diclofenac, as MR1-binding ligands. Some of these ligands inhibited MAIT cells ex vivo and in vivo, while others, including diclofenac metabolites, were agonists...
February 6, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28158922/pulmonary-glass-particles-may-persist-in-the-lung-suppressing-function-of-immune-cells
#15
Eun-Jung Park, Gwang-Hee Lee, Jae-Chan Kim, Sang Jin Lee, Kyuhong Lee, Byoung-Seok Lee, Jaerak Chang, Dong-Wan Kim
The health effects of silica may depend on the inherent properties of crystalline silica or on external factors affecting the biological activity or distribution of its polymorphs. Inhaled crystalline silica is classified as a Group I carcinogen, however, information on the health effects of amorphous silica is still insufficient. Considering that alveolar macrophages play a key role in both innate and adaptive immune responses for removal of foreign bodies that enter via the respiratory system, we treated sheet-like glass particles (SGPs), a type of noncrystalline amorphous silica, to MH-S cells, an alveolar macrophage cell line...
February 3, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28154084/lymphocyte-activation-gene-3-a-novel-therapeutic-target-in-chronic-lymphocytic-leukemia
#16
Mika Shapiro, Yair Herishanu, Ben-Zion Katz, Nili Dezorella, Clare Sun, Sigi Kay, Aaron Polliack, Irit Avivi, Adrian Wiestner, Chava Perry
A novel therapeutic approach in cancer, attempting to stimulate host anti-tumor immunity, involves blocking of immune checkpoints. LAG3 is an immune checkpoint receptor expressed on activated/exhausted T-cells. When engaged by MHC class II molecules, LAG3 negatively regulates T-cell function thereby contributing to tumor escape. Intriguingly, a soluble LAG3 variant activates both immune and malignant MHC class II-presenting cells. In this study, we examined the role of LAG3 in the pathogenesis of chronic lymphocytic leukemia, an MHC class II-presenting malignancy, and show that chronic lymphocytic leukemia cells express and secrete LAG3...
February 2, 2017: Haematologica
https://www.readbyqxmd.com/read/28152048/zika-virus-antagonizes-type-i-interferon-responses-during-infection-of-human-dendritic-cells
#17
James R Bowen, Kendra M Quicke, Mohan S Maddur, Justin T O'Neal, Circe E McDonald, Nadia B Fedorova, Vinita Puri, Reed S Shabman, Bali Pulendran, Mehul S Suthar
Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that is causally linked to severe neonatal birth defects, including microcephaly, and is associated with Guillain-Barre syndrome in adults. Dendritic cells (DCs) are an important cell type during infection by multiple mosquito-borne flaviviruses, including dengue virus, West Nile virus, Japanese encephalitis virus, and yellow fever virus. Despite this, the interplay between ZIKV and DCs remains poorly defined. Here, we found human DCs supported productive infection by a contemporary Puerto Rican isolate with considerable variability in viral replication, but not viral binding, between DCs from different donors...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28148269/dynadom-structure-based-prediction-of-t-cell-receptor-inter-domain-and-t-cell-receptor-peptide-mhc-class-i-association-angles
#18
Thomas Hoffmann, Antoine Marion, Iris Antes
BACKGROUND: T cell receptor (TCR) molecules are involved in the adaptive immune response as they distinguish between self- and foreign-peptides, presented in major histocompatibility complex molecules (pMHC). Former studies showed that the association angles of the TCR variable domains (Vα/Vβ) can differ significantly and change upon binding to the pMHC complex. These changes can be described as a rotation of the domains around a general Center of Rotation, characterized by the interaction of two highly conserved glutamine residues...
February 2, 2017: BMC Structural Biology
https://www.readbyqxmd.com/read/28141543/molecular-challenges-imposed-by-mhc-i-restricted-long-epitopes-on-t-cell-immunity
#19
Tracy M Josephs, Emma J Grant, Stephanie Gras
It has widely been accepted that major histocompatibility complex class I molecules (MHC-I) are limited to binding small peptides of 8 to 10 residues in length. However, this dogma has recently been challenged with the identification of longer peptides (≥11 residues) that can also elicit cytotoxic CD8+ T cell responses. Indeed, a growing number of studies demonstrate that these non-canonical epitopes are important targets for the immune system. As long epitopes represent up to 10% of the peptide repertoire bound to MHC-I molecules, here we review their impact on antigen presentation by MHC-I, TCR recognition, and T cell immunity...
January 31, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28140445/virulence-dependent-induction-of-interleukin-10-producing-tolerogenic-dendritic-cells-by-mycobacterium-tuberculosis-impedes-optimal-th1-proliferation
#20
Hongmin Kim, Kee Woong Kwon, Woo Sik Kim, Sung Jae Shin
Mycobacterium tuberculosis (Mtb) inhibits optimal Th1 responses during infection. However, the precise mechanisms by which virulent Mtb limits Th1 responses remain unclear. Here, we infected dendritic cells (DCs) with the virulent Mtb strain H37Rv or the attenuated strain H37Ra to investigate the phenotypic and functional alterations in DCs and resultant T cell responses. H37Rv-infected DCs suppressed Th1 responses more strongly than H37Ra-infected DCs. Interestingly, H37Rv, but not H37Ra, impaired DC surface molecule (CD80, CD86 and MHC class II) expression due to prominent IL-10 production while augmenting the expression of tolerogenic molecules including PD-L1, CD103, Tim-3, and indoleamine 2,3-dioxygenase (IDO) on DCs in a multiplicity-of-infection-dependent manner...
January 31, 2017: Immunology
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