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https://www.readbyqxmd.com/read/28903331/the-antigenic-identity-of-human-class-i-mhc-phosphopeptides-is-critically-dependent-upon-phosphorylation-status
#1
Fiyaz Mohammed, Daniel H Stones, Angela L Zarling, Carrie R Willcox, Jeffrey Shabanowitz, Kara L Cummings, Donald F Hunt, Mark Cobbold, Victor H Engelhard, Benjamin E Willcox
Dysregulated post-translational modification provides a source of altered self-antigens that can stimulate immune responses in autoimmunity, inflammation, and cancer. In recent years, phosphorylated peptides have emerged as a group of tumour-associated antigens presented by MHC molecules and recognised by T cells, and represent promising candidates for cancer immunotherapy. However, the impact of phosphorylation on the antigenic identity of phosphopeptide epitopes is unclear. Here we examined this by determining structures of MHC-bound phosphopeptides bearing canonical position 4-phosphorylations in the presence and absence of their phosphate moiety, and examining phosphopeptide recognition by the T cell receptor (TCR)...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28900681/regulatory-dendritic-cells
#2
Katsuaki Sato, Tomofumi Uto, Tomohiro Fukaya, Hideaki Takagi
Dendritic cells (DCs) comprise heterogeneous subsets, functionally classified into conventional DCs (cDCs) and plasmacytoid DCs (pDCs). DCs are considered to be essential antigen (Ag)-presenting cells (APCs) that play crucial roles in activation and fine-tuning of innate and adaptive immunity under inflammatory conditions, as well as induction of immune tolerance to maintain immune homeostasis under steady-state conditions. Furthermore, DC functions can be modified and influenced by stimulation with various extrinsic factors, such as ligands for pattern-recognition receptors (PRRs) and cytokines...
September 13, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28894277/host-expression-of-the-cd8-treg-nk-cell-restriction-element-qa-1-is-dispensable-for-transplant-tolerance
#3
Blair T Stocks, Christopher S Wilson, Andrew F Marshall, Lauren A Brewer, Daniel J Moore
Disruption of the non-classical Major Histocompatibility Complex (MHC) Ib molecule Qa-1 impairs CD8 Treg and natural killer (NK) cell function and promotes a lupus-like autoimmune disease. This immune perturbation would be expected to enhance anti-transplant responses and impair tolerance induction, but the effect of Qa-1 deficiency on the transplant response has not been previously reported. Qa-1 deficiency enhanced CD4 TFH and germinal center (GC) B cell numbers in naïve mice and hastened islet allograft rejection...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28892257/candidate-gene-molecular-markers-as-tools-for-analyzing-genetic-susceptibility-to-morbillivirus-infection-in-stranded-cetaceans
#4
Karla Stejskalova, Zuzana Bayerova, Jan Futas, Kristyna Hrazdilova, Marie Klumplerova, Jan Oppelt, Petra Splichalova, Giovanni Di Guardo, Sandro Mazzariol, Cristina Esmeralda Di Francesco, Gabriella Di Francesco, Giuliana Terracciano, Romulus-Marian Paiu, Teodor Dan Ursache, David Modry, Petr Horin
Morbilliviruses, such as Cetacean morbillivirus (CeMV) or Phocine distemper virus (PDV), represent a growing threat for marine mammals on both hemispheres. Since free-ranging animal populations strongly rely on natural resistance mechanisms, innate immunity related genes and virus cell entry receptor genes may represent key factors involved in susceptibility to CeMV in Cetaceans. Using the next generation sequencing technology, we have sequenced eleven candidate genes in two model species, Stenella coeruleoalba and Phocoena phocoena...
September 11, 2017: HLA
https://www.readbyqxmd.com/read/28888143/synthetic-zwitterionic-polysaccharides
#5
REVIEW
Qingju Zhang, Herman S Overkleeft, Gijsbert A van der Marel, Jeroen Dc Codée
Zwitterionic polysaccharides (ZPSs) are a unique class of polysaccharides that are capable of eliciting a T-cell response after being processed by antigen presenting cells and presented on MHC II molecules. In addition, they have also been shown to be potent stimulators of the innate arm of the immune system. To unravel the molecular details of their remarkable immunological activity, various synthetic approaches to assemble fragments towards these polysaccharides have been reported. This review describes these efforts, illustrating the immense challenges presented by these inspiring structures...
September 6, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28881567/restoration-of-immune-surface-molecules-in-kaposi-sarcoma-associated-herpes-virus-infected-cells-by-lenalidomide-and-pomalidomide
#6
David A Davis, Suraj Mishra, Holda A Anagho, Ashley I Aisabor, Prabha Shrestha, Victoria Wang, Yuki Takamatsu, Kenji Maeda, Hiroaki Mitsuya, Jerome B Zeldis, Robert Yarchoan
Kaposi sarcoma-associated herpesvirus (KSHV) is the cause of several tumors, including Kaposi sarcoma and primary effusion lymphoma (PEL). Most viruses have evolved means of escaping immune recognition. KSHV downregulates MHC-I expression during lytic infection, and expression of ICAM-1 and B7-2 (CD86) during latent infection, allowing evasion of T cell and natural killer immunity respectively. These effects are largely mediated by two KSHV-encoded proteins, K3 and K5. We show here that lenalidomide (Len) and pomalidomide (Pom) prevent down-regulation of MHC-I during lytic activation, and restore ICAM-1 and B7-2 surface expression in latently infected PEL cells...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28878119/pharmacologic-hiv-1-nef-blockade-promotes-cd8-t-cell-mediated-elimination-of-latently-hiv-1-infected-cells-in-vitro
#7
Shariq Mujib, Aamir Saiyed, Saleh Fadel, Ardalan Bozorgzad, Nasra Aidarus, Feng Yun Yue, Erika Benko, Colin Kovacs, Lori A Emert-Sedlak, Thomas E Smithgall, Mario A Ostrowski
Eradication of the HIV-1 latent reservoir represents the current paradigm to developing a cure for AIDS. HIV-1 has evolved multiple mechanisms to evade CD8 T cell responses, including HIV-1 Nef-mediated downregulation of MHC-I from the surface of infected cells. Nef transcripts and protein are detectable in samples from aviremic donors, suggesting that Nef expression in latently HIV-1-infected CD4 T cells protects them from immune-mediated clearance. Here, we tested 4 small molecule inhibitors of HIV-1 Nef in an in vitro primary CD4 T cell latency model and measured the ability of autologous ex vivo or HIV-1 peptide-expanded CD8 T cells to recognize and kill latently infected cells as a function of inhibitor treatment...
September 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/28878071/zika-virus-escapes-nk-cell-detection-by-upregulating-mhc-class-i-molecules
#8
Ariella Glasner, Esther Oiknine-Djian, Yiska Weisblum, Mohammad Diab, Amos Panet, Dana G Wolf, Ofer Mandelboim
NK cells are innate lymphocytes that participate in many immune processes encompassing cancer, bacterial and fungal infection, autoimmunity and even pregnancy and are specialize in anti-viral defense. NK cells express inhibitory and activating receptors and kill their targets when activating signals overpower the inhibitory ones. The NK cell inhibitory receptors compose of a uniquely diverse array of proteins named Killer-cell immunoglobulin-like receptors (KIRs) the CD94 family and the leukocyte immunoglobulin like receptor family (LIR)...
September 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28877980/nad-metabolism-fuels-human-and-mouse-intestinal-inflammation
#9
Romana R Gerner, Victoria Klepsch, Sophie Macheiner, Kathrin Arnhard, Timon E Adolph, Christoph Grander, Verena Wieser, Alexandra Pfister, Patrizia Moser, Natascha Hermann-Kleiter, Gottfried Baier, Herbert Oberacher, Herbert Tilg, Alexander R Moschen
OBJECTIVE: Nicotinamide phosphoribosyltransferase (NAMPT, also referred to as pre-B cell colony-enhancing factor or visfatin) is critically required for the maintenance of cellular nicotinamide adenine dinucleotide (NAD) supply catalysing the rate-limiting step of the NAD salvage pathway. NAMPT is strongly upregulated in inflammation including IBD and counteracts an increased cellular NAD turnover mediated by NAD-depleting enzymes. These constitute an important mechanistic link between inflammatory, metabolic and transcriptional pathways and NAD metabolism...
September 6, 2017: Gut
https://www.readbyqxmd.com/read/28875066/genes-of-the-major-histocompatibility-complex-highlight-interactions-of-the-innate-and-adaptive-immune-system
#10
Barbara Lukasch, Helena Westerdahl, Maria Strandh, Hans Winkler, Yoshan Moodley, Felix Knauer, Herbert Hoi
BACKGROUND: A well-functioning immune defence is crucial for fitness, but our knowledge about the immune system and its complex interactions is still limited. Major histocompatibility complex (MHC) molecules are involved in T-cell mediated adaptive immune responses, but MHC is also highly upregulated during the initial innate immune response. The aim of our study was therefore to determine to what extent the highly polymorphic MHC is involved in interactions of the innate and adaptive immune defence and if specific functional MHC alleles (FA) or heterozygosity at the MHC are more important...
2017: PeerJ
https://www.readbyqxmd.com/read/28872140/purification-of-the-membrane-compartment-for-endoplasmic-reticulum-associated-degradation-of-exogenous-antigens-in-cross-presentation
#11
Jun Imai, Mayu Otani, Takahiro Sakai, Shinichi Hatta
Dendritic cells (DCs) are highly capable of processing and presenting internalized exogenous antigens upon major histocompatibility class (MHC) I molecules also known as cross-presentation (CP). CP plays an important role not only in the stimulation of naïve CD8(+) T cells and memory CD8(+) T cells for infectious and tumor immunity but also in the inactivation of self-acting naïve T cells by T cell anergy or T cell deletion. Although the critical molecular mechanism of CP remains to be elucidated, accumulating evidence indicates that exogenous antigens are processed through endoplasmic reticulum-associated degradation (ERAD) after export from non-classical endocytic compartments...
August 21, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28866275/mhc-class-ii-alpha-beta-and-mhc-class-ii-associated-invariant-chains-from-chinese-sturgeon-acipenser-sinensis-and-their-response-to-immune-stimulation
#12
Xiuyu Li, Hejun Du, Liu Liu, Xiuling You, Mingjiang Wu, Zhiyong Liao
The major histocompatibility complex class II (MHC II) molecules play a vital role in adaptive immune response through presenting antigenic peptides to CD4(+) T lymphocytes. To accomplish this physiologic function, the MHC class II-associated invariant chain interacts with the MHC II α/β subunits and promotes their correct assembly and efficient traffic. Here, we isolated the cDNAs of MHC II α, β and MHC II-associated invariant chains (designated as CsMHC II α, CsMHC II β, and CsMHC II γ) from Chinese sturgeon (Acipenser sinensis)...
August 31, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28860950/t-cell-s-sense-of-self-a-role-of-self-recognition-in-shaping-functional-competence-of-na%C3%A3-ve-t-cells
#13
REVIEW
Hee-Ok Kim, Jae-Ho Cho
Post-thymic naïve T cells constitute a key cellular arm of adaptive immunity, with a well-known characteristic of the specificity and robustness of responses to cognate foreign antigens which is presented as a form of antigen-derived peptides bound to major histocompatibility complex (MHC) molecules by antigen-presenting cells (APCs). In a steady state, however, these cells are resting, quiescent in their activity, but must keep full ranges of functional integrity to mount rapid and robust immunity to cope with various infectious pathogens at any time and space...
August 2017: Immune Network
https://www.readbyqxmd.com/read/28860189/the-major-histocompatibility-complex-class-i-immunopeptidome-of-extracellular-vesicles
#14
Silvia A Synowsky, Sally L Shirran, Fiona G M Cooke, Antony N Antoniou, Catherine H Botting, Simon J Powis
Extracellular vesicles (EVs) are released by most cell types and have been associated with multiple immunomodulatory functions. MHC class I molecules have crucial roles in antigen presentation and in eliciting immune responses and are known to be incorporated into EVs. However, the MHC class I immunopeptidome of EVs has not been established. Here, using a small-scale immunoisolation of the antigen serotypes HLA-A*02:01 and HLA-B*27:05 expressed on the Epstein-Barr virus-transformed B cell line Jesthom and MS of the eluted peptides from both cells and EVs, we identified 516 peptides that bind either HLA-A*02:01 or HLA-B*27:05...
August 31, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28855904/immunological-properties-of-murine-parthenogenetic-stem-cell-derived-cardiomyocytes-and-engineered-heart-muscle
#15
Michael Didié, Satish Galla, Vijayakumar Muppala, Ralf Dressel, Wolfram-Hubertus Zimmermann
Pluripotent parthenogenetic stem cells (pSCs) can be derived by pharmacological activation of unfertilized oocytes. Homozygosity of the major histocompatibility complex (MHC) in pSCs makes them an attractive cell source for applications in allogeneic tissue repair. This was recently demonstrated for pSC-based tissue-engineered heart repair. A detailed analysis of immunological properties of pSC-derived cardiomyocytes and engineered heart muscle (EHM) thereof is, however, lacking. The aim of this study was to determine baseline and cytokine-inducible MHC class I and MHC class II as well as programmed death ligand-1 (PDL-1) and co-stimulatory protein (CD40, CD80, CD86) expression in pSC-derived cardiomyocytes and pSC-EHM in vitro and in vivo...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28841693/the-effect-of-aqueous-extract-of-xinjiang-artemisia-rupestris-l-an-influenza-virus-vaccine-adjuvant-on-enhancing-immune-responses-and-reducing-antigen-dose-required-for-immunity
#16
Ailian Zhang, Danyang Wang, Jinyao Li, Feng Gao, Xucheng Fan
Potent adjuvant can improve the effectiveness of vaccines and reduce the antigen doses required for initiating the protective immunity. In this study, we identified that aqueous extract of Artemisia rupestris L. (AEAR) could be employed as an efficient adjuvant for influenza virus vaccine (V) to enhance immune responses and reduce the antigen doses required for initiating immunity, without compromising the immune response. ICR mice were subcutaneously co-administrated with V combined with different concentrations of AEAR demonstrated that 300 μg AEAR could significantly improve hemagglutination inhibition (HI) and increase IgG antibody titers in serum (P<0...
2017: PloS One
https://www.readbyqxmd.com/read/28835358/combined-action-of-human-commensal-bacteria-and-amorphous-silica-nanoparticles-on-the-viability-and-immune-responses-of-dendritic-cells
#17
Giulia Malachin, Elisa Lubian, Fabrizio Mancin, Emanuele Papini, Regina Tavano
Dendritic cells (DCs) regulate the host-microbe balance in gut and skin, tissues likely exposed to nanoparticles (NPs) present in drugs, food and cosmetics. We analysed the viability and the activation of DCs incubated with extracellular media (EMs) obtained from cultures of commensal (E. coli, S. epidermidis) or pathogenic (P. aeruginosa, S. aureus) bacteria, in the presence of amorphous silica nanoparticles (SiO2-NPs). EMs synergised cytotoxicity and cytokines production with different nanoparticle dose-response characteristics, depending on the bacterial species...
August 23, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28831637/in-vivo-immunological-properties-research-on-mesenchymal-stem-cells-based-engineering-cartilage-by-a-dialyzer-pocket-model
#18
Tun Yuan, Hongrong Luo, Likun Guo, Hongsong Fan, Jie Liang, Yujiang Fan, Xingdong Zhang
As the seed cells, the immune properties of the mesenchymal stem cells are important for the tissue engineering restoring effect. But the in vivo research model is lacking. In the study, based on a dialyzer pocket model, changes in immunological properties and the differentiation of seeded mesenchymal stem cells (MSCs) in collagen hydrogel were studied in muscle and articular cavity implantation, respectively. The results showed that collagen hydrogel can induce MSCs to form cartilage tissue, followed by alteration of immunological properties...
August 22, 2017: Journal of Materials Science. Materials in Medicine
https://www.readbyqxmd.com/read/28817603/expression-of-the-mhc-class-ii-in-triple-negative-breast-cancer-is-associated-with-tumor-infiltrating-lymphocytes-and-interferon-signaling
#19
In Ah Park, Seong-Hye Hwang, In Hye Song, Sun-Hee Heo, Young-Ae Kim, Won Seon Bang, Hye Seon Park, Miseon Lee, Gyungyub Gong, Hee Jin Lee
Tumor-infiltrating lymphocytes (TILs) have been known for their strong prognostic and predictive significance in triple-negative breast cancer (TNBC). Several mechanisms for TIL influx in TNBC have been elucidated. Major histocompatibility complex class II (MHC-II) is an essential component of the adaptive immune system and is generally restricted to the surface of antigen-presenting cells. However, it has been reported that interferon-gamma signaling may induce MHC-II in almost all cell types, including those derived from cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28811364/mechanosensing-drives-acuity-of-%C3%AE-%C3%AE-t-cell-recognition
#20
Yinnian Feng, Kristine N Brazin, Eiji Kobayashi, Robert J Mallis, Ellis L Reinherz, Matthew J Lang
T lymphocytes use surface [Formula: see text] T-cell receptors (TCRs) to recognize peptides bound to MHC molecules (pMHCs) on antigen-presenting cells (APCs). How the exquisite specificity of high-avidity T cells is achieved is unknown but essential, given the paucity of foreign pMHC ligands relative to the ubiquitous self-pMHC array on an APC. Using optical traps, we determine physicochemical triggering thresholds based on load and force direction. Strikingly, chemical thresholds in the absence of external load require orders of magnitude higher pMHC numbers than observed physiologically...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
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