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https://www.readbyqxmd.com/read/28317931/recruitment-of-bone-marrow-cd11b-gr-1-cells-by-polymeric-nanoparticles-for-antigen-cross-presentation
#1
Ya-Wun Yang, Wen-Hui Luo
The objective of this study was to investigate the function of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) on the activation of antigen-specific CD8(+) T cell responses via the CD11b(+)Gr(-)1(+) myeloid subpopulations in murine bone marrow (BM). PLGA NPs containing ovalbumin (OVA) were fabricated by the double-emulsion method. The CD11b(+)Gr-1(low)Ly-6C(high) and CD11b(+)Gr-1(high)Ly-6C(low) subsets from mice bone marrow were sorted and treated with the PLGA/OVA NPs, followed by co-culture with the carboxyfluorescein succinimidyl ester (CFSE)-labelled OT-I CD8(+) cells...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28315936/peptide-binding-motifs-of-two-common-equine-class-i-mhc-molecules-in-thoroughbred-horses
#2
Tobias Bergmann, Mikaela Lindvall, Erin Moore, Eugene Moore, John Sidney, Donald Miller, Rebecca L Tallmadge, Paisley T Myers, Stacy A Malaker, Jeffrey Shabanowitz, Nikolaus Osterrieder, Bjoern Peters, Donald F Hunt, Douglas F Antczak, Alessandro Sette
Quantitative peptide-binding motifs of MHC class I alleles provide a valuable tool to efficiently identify putative T cell epitopes. Detailed information on equine MHC class I alleles is still very limited, and to date, only a single equine MHC class I allele, Eqca-1*00101 (ELA-A3 haplotype), has been characterized. The present study extends the number of characterized ELA class I specificities in two additional haplotypes found commonly in the Thoroughbred breed. Accordingly, we here report quantitative binding motifs for the ELA-A2 allele Eqca-16*00101 and the ELA-A9 allele Eqca-1*00201...
March 18, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28314956/evolution-of-mhc-based-technologies-used-for-detection-of-antigen-responsive-t-cells
#3
REVIEW
Amalie Kai Bentzen, Sine Reker Hadrup
T cell-mediated recognition of peptide-major histocompatibility complex (pMHC) class I and II molecules is crucial for the control of intracellular pathogens and cancer, as well as for stimulation and maintenance of efficient cytotoxic responses. Such interactions may also play a role in the development of autoimmune diseases. Novel insights into this mechanism are crucial to understanding disease development and establishing new treatment strategies. MHC multimers have been used for detection of antigen-responsive T cells since the first report by Altman et al...
March 17, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28314751/identification-of-glycopeptides-as-post-translationally-modified-neoantigens-in-leukemia
#4
Stacy A Malaker, Sarah A Penny, Lora G Steadman, Paisley T Myers, Justin Loke, Manoj Raghavan, Dina L Bai, Jeffery Shabanowitz, Donald Hunt, Mark Cobbold
Leukemias are highly immunogenic but have a low mutational load, providing few mutated peptide targets. Thus, the identification of alternative neoantigens is a pressing need. Here, we identify 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications as candidate neoantigens, using three experimental approaches. Thirteen of these peptides were also detected with disaccharide units on the same residues and two contain either mono- and/or di-methylated arginine residues...
March 17, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28299193/recent-advances-in-major-histocompatibility-complex-mhc-class-i-antigen-presentation-plastic-mhc-molecules-and-tapbpr-mediated-quality-control
#5
REVIEW
Andy van Hateren, Alistair Bailey, Tim Elliott
We have known since the late 1980s that the function of classical major histocompatibility complex (MHC) class I molecules is to bind peptides and display them at the cell surface to cytotoxic T cells. Recognition by these sentinels of the immune system can lead to the destruction of the presenting cell, thus protecting the host from pathogens and cancer. Classical MHC class I molecules (MHC I hereafter) are co-dominantly expressed, polygenic, and exceptionally polymorphic and have significant sequence diversity...
2017: F1000Research
https://www.readbyqxmd.com/read/28294313/suppression-of-murine-tumor-growth-through-cd8-ctls-via-activated-dec-205-dendritic-cells-by-sequential-administration-of-%C3%AE-galactosylceramide-in-vivo
#6
Hideki Kogo, Masumi Shimizu, Yasuyuki Negishi, Fiji Uchida, Hidemi Takahashi
Cancer immunity is mediated through the effective priming and activation of tumor-specific class I major histocompatibility complex (MHC-I) molecule-restricted CD8(+) cytotoxic T lymphocytes (CTLs). DEC-205(+) dendritic cells (DCs) can cross-present the epitope(s) of captured tumor antigens associated with class I MHC molecules alongside co-stimulatory molecules to prime and activate tumor-specific CD8(+) CTLs. Immunosuppressive tolerogenic DCs with reduced co-stimulatory molecules may be a cause of impaired CTL induction...
March 12, 2017: Immunology
https://www.readbyqxmd.com/read/28292965/repurposed-jak1-jak2-inhibitor-reverses-established-autoimmune-insulitis-in-non-obese-diabetic-mice
#7
Prerak M Trivedi, Kate L Graham, Nicholas A Scott, Misty R Jenkins, Suktilang Majaw, Robyn M Sutherland, Stacey Fynch, Andrew M Lew, Christopher J Burns, Balasubramanian Krishnamurthy, Thomas C Brodnicki, Stuart I Mannering, Thomas W Kay, Helen E Thomas
Recent advances in immunotherapeutics have not yet changed the routine management of autoimmune type 1 diabetes. There is an opportunity to repurpose therapeutics from other diseases to type 1 diabetes, especially when there is evidence for overlapping mechanisms. JAK1/JAK2 inhibitors are in development or clinical use for indications including rheumatoid arthritis. There is good evidence for activation of the JAK1/JAK2 and STAT1 pathway in human type 1 diabetes and in mouse models, especially in beta cells...
March 14, 2017: Diabetes
https://www.readbyqxmd.com/read/28290659/protein-a-functionalized-polyelectrolyte-microcapsules-as-universal-platform-for-enhanced-targeting-of-cell-surface-receptors
#8
Tatiana A Kolesnikova, Gayane Kiragosyan, Trang H N Le, Sebastian Springer, Mathias Winterhalter
Targeted delivery systems recognizing specific receptors are a key element in personalized medicine. Such systems allow the delivery of therapeutics to desired sites of the body, increasing their local concentration and thus reducing the side effects. In this study, we fabricate chemically crosslinked (PAH/PAA)2 microcapsules coated with specific cell-targeting antibodies in random (via direct covalent coupling to the surface) or optimized (via supporting layer of protein A) orientation. We use these antibody-functionalized capsules to target major histocompatibility complex (MHC) class I receptors in living cells, and quantify the efficiency of targeting by flow cytometry...
March 14, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28289410/autophagy-and-autophagy-related-proteins-in-cns-autoimmunity
#9
REVIEW
Christian W Keller, Jan D Lünemann
Autophagy comprises a heterogeneous group of cellular pathways that enables eukaryotic cells to deliver cytoplasmic constituents for lysosomal degradation, to recycle nutrients, and to survive during starvation. In addition to these primordial functions, autophagy has emerged as a key mechanism in orchestrating innate and adaptive immune responses and to shape CD4(+) T cell immunity through delivery of peptides to major histocompatibility complex (MHC) class II-containing compartments (MIICs). Individual autophagy proteins additionally modulate expression of MHC class I molecules for CD8(+) T cell activation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28287107/dying-cells-actively-regulate-adaptive-immune-responses
#10
REVIEW
Nader Yatim, Sean Cullen, Matthew L Albert
Dying cells have an important role in the initiation of CD8(+) T cell-mediated immunity. The cross-presentation of antigens derived from dying cells enables dendritic cells to present exogenous tissue-restricted or tumour-restricted proteins on MHC class I molecules. Importantly, this pathway has been implicated in multiple autoimmune diseases and accounts for the priming of tumour antigen-specific T cells. Recent data have revealed that in addition to antigen, dying cells provide inflammatory and immunogenic signals that determine the efficiency of CD8(+) T cell cross-priming...
March 13, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28280496/cd4-ctl-a-cytotoxic-subset-of-cd4-t-cells-their-differentiation-and-function
#11
REVIEW
Arata Takeuchi, Takashi Saito
CD4(+) T cells with cytotoxic activity (CD4 CTL) have been observed in various immune responses. These cells are characterized by their ability to secrete granzyme B and perforin and to kill the target cells in an MHC class II-restricted fashion. Although CD4 CTLs were once thought to be an in vitro artifact associated with long-term culturing, they have since been identified in vivo and shown to play important roles in antiviral and antitumor immunity, as well as in inflammation. Functional characterization of CD4 CTL suggests their potential significance for therapeutic purposes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28279639/corrigendum-to-genetics-variants-and-serum-levels-of-mhc-class-i-chain-related-a-in-predicting-hepatocellular-carcinoma-development-in-chronic-hepatitis-c-patients-post-antiviral-treatment-ebiomedicine-15-2017-81-89
#12
Chung-Feng Huang, Ching-I Huang, Ming-Lun Yeh, Shu-Chi Wang, Kuan-Yu Chen, Yu-Min Ko, Ching-Chih Lin, Yi-Shan Tsai, Pei-Chien Tsai, Zu-Yau Lin, Shinn-Cherng Chen, Chia-Yen Dai, Jee-Fu Huang, Wan-Long Chuang, Ming-Lung Yu
No abstract text is available yet for this article.
March 1, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28278760/computational-characterization-of-residue-couplings-and-micropolymorphism-induced-changes-in-the-dynamics-of-two-differentially-disease-associated-human-mhc-class-i-alleles
#13
Onur Serçinoğlu, Pemra Ozbek
Human major histocompatibility complex class I (MHC I) - or human leukocyte antigen (HLA) - proteins present intracellularly processed peptides to cytotoxic T lymphocytes in the adaptive immune response to pathogens. A high level of polymorphism in human MHC I proteins defines the peptide-binding specificity of thousands of different MHC alleles. However, polymorphism as well as the peptide ligand can also affect the global dynamics of the complex. In this study, we conducted classical molecular dynamics simulations of two HLA alleles, the ankylosing spondylitis (AS) associated/tapasin-dependent HLA-B*27:05 and nondisease-associated/tapasin-independent HLA-B*27:09, both in peptide-free forms as well as complex with four different peptides ligands...
March 1, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28278207/pa28-modulates-antigen-processing-and-viral-replication-during-coxsackievirus-b3-infection
#14
Dorota Respondek, Martin Voss, Ina Kühlewindt, Karin Klingel, Elke Krüger, Antje Beling
The function of the proteasome is modulated at the level of subunit expression and by association with its regulatory complexes. During coxsackievirus B3 (CVB3) myocarditis, IFN-induced formation of immunoproteasomes (ip) is known to be critical for regulating immune modulating molecules. The function of the IFN-γ-inducible proteasome regulator subunits PA28 α and β, however, in this context was unknown. During viral myocarditis, we found an increased abundance of PA28β subunits in heart tissue. PA28α/β exists in PA28-20S-PA28 and PA700-20S-PA28 hybrid proteasome complexes in cells both with either predominant ip and standard proteasome (sp) expression...
2017: PloS One
https://www.readbyqxmd.com/read/28277746/genetic-variation-of-mhc-class-i-polymorphic-alu-insertions-poalins-in-three-subpopulations-of-the-east-midlands-uk
#15
Sarabjit S Mastana, Jasvinder S Bhatti, Puneetpal Singh, Adam Wiles, Jonathan Holland
BACKGROUND: Alu elements are highly researched due to their useful nature as markers in the study of human population genetics. Recently discovered Major Histocompatibility Complex (MHC) polymorphic Alu insertions (POALINs) have not been examined extensively for genetic variation and their HLA associations. AIMS: The aim of this study is to assess the genetic variation between three populations using five recently discovered POALINs. METHODS AND SUBJECTS: The study examined 190 healthy, unrelated subjects from three different populations in the East Midlands (UK) for the presence or absence of five Alu elements (AluHG, AluMICB, AluHJ, AluTF and AluHF) via the polymerase chain reaction followed by gel electrophoresis...
March 5, 2017: Annals of Human Biology
https://www.readbyqxmd.com/read/28274545/tumour-and-placenta-establishment-the-importance-of-antigen-processing-and-presentation
#16
Emma Reeves, Edward James
Classical and non-classical MHC class I (MHC I) molecules displayed at the cell surface are essential for the induction of innate and adaptive immune responses. Classical MHC I present endogenously derived peptides to CD8(+) T cells for immunosurveillance of infected or malignant cells. By contrast, non-classical MHC I, in particular HLA-G, also display peptides, but primarily act as immunomodulatory ligands for the innate immune response and are an important component for extravillous trophoblast invasion to form the placenta in pregnancy...
February 28, 2017: Placenta
https://www.readbyqxmd.com/read/28274199/properties-of-stat1-and-irf1-enhancers-and-the-influence-of-snps
#17
Mohamed Abou El Hassan, Katherine Huang, Manoja B K Eswara, Zhaodong Xu, Tao Yu, Arthur Aubry, Zuyao Ni, Izzy Livne-Bar, Monika Sangwan, Mohamad Ahmad, Rod Bremner
BACKGROUND: STAT1 and IRF1 collaborate to induce interferon-γ (IFNγ) stimulated genes (ISGs), but the extent to which they act alone or together is unclear. The effect of single nucleotide polymorphisms (SNPs) on in vivo binding is also largely unknown. RESULTS: We show that IRF1 binds at proximal or distant ISG sites twice as often as STAT1, increasing to sixfold at the MHC class I locus. STAT1 almost always bound with IRF1, while most IRF1 binding events were isolated...
March 9, 2017: BMC Molecular Biology
https://www.readbyqxmd.com/read/28273384/computational-prediction-of-usutu-virus-e-protein-b-cell-and-t-cell-epitopes-for-potential-vaccine-development
#18
Navaneethan Palanisamy, Johan Lennerstrand
Usutu virus (family Flaviviridae), once confined to Africa, has emerged in Europe a decade ago. The virus has been spreading throughout Europe at a greater pace mostly affecting avian species. While most bird species remain asymptomatic carriers of this virus, few bird species are highly susceptible. Lately, Usutu virus (USUV) infections in humans were reported sporadically with severe neuroinvasive symptoms like meningoencephalitis. Since so much is unknown about this virus, which potentially may cause severe diseases in humans, there is a need for more studies of this virus...
March 8, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28270092/validation-of-t-track%C3%A2-cmv-to-assess-the-functionality-of-cytomegalovirus-reactive-cell-mediated-immunity-in-hemodialysis-patients
#19
Bernhard Banas, Carsten A Böger, Gerhard Lückhoff, Bernd Krüger, Sascha Barabas, Julia Batzilla, Mathias Schemmerer, Josef Köstler, Hanna Bendfeldt, Anne Rascle, Ralf Wagner, Ludwig Deml, Joachim Leicht, Bernhard K Krämer
BACKGROUND: Uncontrolled cytomegalovirus (CMV) replication in immunocompromised solid-organ transplant recipients is a clinically relevant issue and an indication of impaired CMV-specific cell-mediated immunity (CMI). Primary aim of this study was to assess the suitability of the immune monitoring tool T-Track® CMV to determine CMV-reactive CMI in a cohort of hemodialysis patients representative of patients eligible for renal transplantation. Positive and negative agreement of T-Track® CMV with CMV serology was examined in 124 hemodialysis patients, of whom 67 (54%) revealed a positive CMV serostatus...
March 7, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28265272/enforced-ox40-stimulation-empowers-booster-vaccines-to-induce-effective-cd4-and-cd8-t-cell-responses-against-mouse-cytomegalovirus-infection
#20
Eleni Panagioti, Louis Boon, Ramon Arens, Sjoerd H van der Burg
There is an imperative need for effective preventive vaccines against human cytomegalovirus as it poses a significant threat to the immunologically immature, causing congenital disease, and to the immune compromised including transplant recipients. In this study, we examined the efficacy of synthetic long peptides (SLPs) as a CD4(+) and CD8(+) T cell-eliciting preventive vaccine approach against mouse CMV (MCMV) infection. In addition, the use of agonistic OX40 antibodies to enhance vaccine efficacy was explored...
2017: Frontiers in Immunology
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