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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/28218509/critical-role-of-inter-domain-interactions-on-the-conformational-change-and-catalytic-mechanism-of-endoplasmic-reticulum-aminopeptidase-1
#2
Athanasios Stamogiannos, Zachary Maben, Athanasios Papakyriakou, Anastasia Mpakali, Paraskevi Kokkala, Dimitris Georgiadis, Lawrence J Stern, Efstratios Stratikos
Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) is an intracellular enzyme important for the generation of antigenic epitopes and class I MHC-restricted adaptive immune responses. ERAP1 processes a vast variety of different peptides but still shows length and sequence selectivity although the mechanism behind these properties is poorly understood. X-ray crystallographic analysis has revealed that ERAP1 can assume at least two distinct conformations in which the C-terminal domain IV is either proximal or distal to the active site domain II...
February 20, 2017: Biochemistry
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/28214886/adenovirus-vector-harboring-the-hbcag-and-tripeptidyl-peptidase-ii-genes-induces-potent-cellular-immune-responses-in-vivo
#4
Quanhui Tan, Siyuan Ma, Jianjun Hu, Xiaohua Chen, Yongsheng Yu, Zhenghao Tang, Guoqin Zang
BACKGROUND: Chronic hepatitis B virus (HBV) infection is associated with a weak but specific cellular immune response of the host to HBV. Tripeptidyl peptidaseⅡ (TPPⅡ), an intracellular macromolecule and proteolytic enzyme, plays an important complementary and compensatory role for the proteasome during viral protein degradation and major histocompatibility complex class I antigen presentation by inducing a specific cellular immune response in vivo. Based on a previous study, we aimed to explore the role of MHC class I antigen presentation in vivo and the mechanisms that may be involved...
January 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28213472/%C3%AE-2-microglobulin-participates-in-development-of-lung-emphysema-by-inducing-lung-epithelial-cells-senescence
#5
Na Gao, Ying Wang, Chun-Ming Zheng, Yan-Li Gao, Hui Li, Yan Li, Ting-Ting Fu, Li-Li Xu, Wei Wang, Sun Ying, Kewu Huang
β2-microglobulin (β2m), the light chain of major histocompatibility complex class 1 (MHC I), has been identified as a pro-aging factors and involved in the pathogenesis of neurodegenerative disorders by driving cognitive and regenerative impairments. However, little attention has focused on the effect of β2m in development of lung emphysema. Here, we found that concentrations of β2m in plasma were significantly elevated in patients with lung emphysema than those in normal control subjects (1.89 ± 0.12 mg/l vs 1...
February 17, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28210263/a-paradigm-shift-on-the-question-of-b-cells-in-transplantation-recent-insights-on-regulating-the-alloresponse
#6
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/28202532/cd40-signaling-drives-potent-cellular-immune-responses-in-heterologous-cancer-vaccinations
#7
Supot Nimanong, Dmitrij Ostroumov, Jessica Wingerath, Sarah Knocke, Norman Woller, Engin Guerlevik, Christine Falk, Michael P Manns, Florian Kuehnel, Thomas C Wirth
Antagonistic antibodies targeting co-inhibitory receptors have revolutionized the treatment of cancer by inducing durable immune responses and clinical remissions in patients. In contrast, success of agonistic costimulatory antibodies has thus far been limited due to insufficient induction of adaptive immune responses. Here we describe a novel vaccination method consisting of a primary dendritic cell immunization followed by a composite vaccination including an agonistic CD40 antibody, soluble antigen and a TLR3 agonist, referred to as CoAT...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28202460/t-regulatory-cells-and-dendritic-cells-protect-against-transfusion-related-acute-lung-injury-via-il-10
#8
Rick Kapur, Michael Kim, Rukhsana Aslam, Mark J McVey, Arata Tabuchi, Alice Luo, Jonathan Liu, Yuan Li, Shanjeevan Shanmugabhavananthan, Edwin R Speck, Anne Zufferey, George Yousef, Haibo Zhang, Mathew T Rondina, Andrew S Weyrich, Leendert Porcelijn, Wolfgang M Kuebler, Arthur S Slutsky, John W Semple
Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related fatalities and is characterized by acute respiratory distress following blood transfusion. Donor antibodies are frequently involved, however, the pathogenesis and protective mechanisms in the recipient are poorly understood and specific therapies are lacking. Using newly developed murine TRALI models based on injection of anti-MHC class I antibodies, we found CD4+CD25+FoxP3+ T-regulatory cells (Tregs) and CD11c+ dendritic cells (DCs) to be critical effectors that protect against TRALI...
February 15, 2017: Blood
https://www.readbyqxmd.com/read/28199391/correction-correction-correction-influenza-virus-targets-class-i-mhc-educated-nk-cells-for-immunoevasion
#9
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.ppat.1006105.].
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28197373/systemic-activation-of-antigen-presenting-cells-via-rna-loaded-nanoparticles
#10
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/28191644/nk-cell-receptors-nkp46-and-ncr1-control-human-metapneumovirus-infection
#11
Mohammad Diab, Ariella Glasner, Batya Issacson, Yotam Bar-On, Yaron Drori, Rachel Yamin, Alexandra Duev-Cohen, Oded Danziger, Rachel Zamostiano, Michal Mandelboim, Stipan Jonjic, Eran Bacharach, Ofer Mandelboim
Natural killer (NK) cells are capable of killing various pathogens upon stimulation of activating receptors. Human metapneumovirus (HMPV) is a respiratory virus, which was discovered in 2001 and is responsible for acute respiratory tract infection in infants and children worldwide. HMPV infection is very common, infecting around 70% of all children under the age of five. Under immune suppressive conditions, HMPV infection can be fatal. Not much is known on how NK cells respond to HMPV. In this study, using reporter assays and NK-cell cytotoxicity assays performed with human and mouse NK cells, we demonstrated that the NKp46 activating receptor and its mouse orthologue Ncr1, both members of the NCR family, recognized an unknown ligand expressed by HMPV infected human cells...
February 13, 2017: European Journal of Immunology
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
#12
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/28184299/the-role-of-cdc1s-in-vivo-cd8-t-cell-priming-through-cross-presentation
#13
REVIEW
Derek Theisen, Kenneth Murphy
The cDC1 subset of classical dendritic cells is specialized for priming CD8 T cell responses through the process of cross-presentation. The molecular mechanisms of cross-presentation remain incompletely understood because of limited biochemical analysis of rare cDC1 cells, difficulty in their genetic manipulation, and reliance on in vitro systems based on monocyte- and bone-marrow-derived dendritic cells. This review will discuss cross-presentation from the perspective of studies with monocyte- or bone-marrow-derived dendritic cells while highlighting the need for future work examining cDC1 cells...
2017: F1000Research
https://www.readbyqxmd.com/read/28179428/breaking-confinement-unconventional-peptide-presentation-by-major-histocompatibility-mhc-class-i-allele-hla-a-02-01
#14
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/28166217/drugs-and-drug-like-molecules-can-modulate-the-function-of-mucosal-associated-invariant-t-cells
#15
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/28161407/a-novel-mutation-in-tap1-gene-leading-to-mhc-class-i-deficiency-report-of-two-cases-and-review-of-the-literature
#16
Damla Hanalioglu, Deniz Cagdas Ayvaz, Tuba Turul Ozgur, Mirjam van der Burg, Ozden Sanal, Ilhan Tezcan
Major histocompatibility complex (MHC) class I deficiency syndrome is a rare primary immunodeficiency caused by mutations in the peptide transporter complex associated with antigen presentation (TAP) gene which plays a crucial role in intracellular peptide antigen presentation. A few cases have been reported to date. Recurrent sinopulmonary infections and skin ulcers are main characteristics of the syndrome. Here we report two siblings diagnosed with TAP1 deficiency syndrome associated only with recurrent sinopulmonary infections with the description of a novel mutation leading to a premature stop codon in TAP1 gene and review of the relevant literature...
February 1, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28159899/cross-presentation-of-soluble-and-cell-associated-antigen-by-murine-hepatocytes-is-enhanced-by-collectrin-expression
#17
Joseph S Dolina, Sylvia Cechova, Christine K Rudy, Sun-Sang J Sung, William W Tang, Joey Lee, Young S Hahn, Thu H Le
Cross-presentation is a modular series of intracellular events dictating the internalization and subsequent MHC class I (MHC I) display of extracellular Ags. This process has been defined in dendritic cells and plays a fundamental role in the induction of CD8(+) T cell immunity during viral, intracellular bacterial, and antitumor responses. Herein, acute viral infection of murine liver with adenovirus, a model for intrahepatic cross-presentation, confirms hepatocytes directly contribute to cross-presentation of Ags and priming the pool of naive CD8(+) T cells within the liver microenvironment...
February 3, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28159300/attenuation-of-alpha-naphthylisothiocyanate-anit-induced-biliary-fibrosis-by-depletion-of-hepatic-macrophages-in-rats
#18
Hossain M Golbar, Takeshi Izawa, Alexandra Bondoc, Kavindra K Wijesundera, Anusha H Tennakoon, Mitsuru Kuwamura, Jyoji Yamate
Biliary fibrosis is a complex process in which macrophages and myofibroblasts may play central roles. We investigated biliary fibrosis lesions induced in the Glisson's sheath in rats by alpha-naphthylisothiocyanate (ANIT) administration under macrophage depletion. Hepatic macrophages were depleted in F344 rats with liposome-encapsulated clodronate (CLD) (10mL/kg body weight, i.v) followed by bile duct injury with ANIT (75mg/kg body weight, i.p) (ANIT+CLD group). Rats received empty-liposomes (Lipo) followed by ANIT, and served as control (ANIT+Lipo group)...
January 31, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/28158922/pulmonary-glass-particles-may-persist-in-the-lung-suppressing-function-of-immune-cells
#19
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/28154890/single-nucleotide-polymorphisms-in-the-fc%C3%AE-r3a-and-tap1-genes-impact-adcc-in-cynomolgus-monkey-pbmcs
#20
Jonathan C Sanford, Hong Wu, Yasmina Abdiche, Julie A Harney, Javier Chaparro-Riggers, Karissa Adkins
Phenotypic variability is often observed in cynomolgus monkeys on preclinical studies and may, in part, be driven by genetic variability. However, the role of monkey genetic variation remains largely unexplored in the context of drug response. This study evaluated genetic variation in cynomolgus monkey FcγR3A and TAP1 genes and the potential impact of identified polymorphisms on antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro. Studies in humans have demonstrated that a single nucleotide polymorphism (SNP), F158V, in FcγR3A can influence response to rituximab through altered ADCC and that SNPs in TAP1/2 decrease natural killer (NK) cell activity against major histocompatibility complex (MHC) class I deficient cells, potentially through altered ADCC...
February 3, 2017: Immunogenetics
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