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Lorenz Jahn, Dirk M van der Steen, Renate S Hagedoorn, Pleun Hombrink, Michel G D Kester, Marjolein P Schoonakker, Daniëlle de Ridder, Peter A van Veelen, J H Frederik Falkenburg, Mirjam H M Heemskerk
Immunotherapy of B-cell leukemia and lymphoma with CD20-targeting monoclonal antibodies (mAbs) has demonstrated clinical efficacy. However, the emergence of unresponsive disease due to low or absent cell surface CD20 urges the need to develop additional strategies. In contrast to mAbs, T-cells via their T-cell receptor (TCR) can recognize not only extracellular but also intracellular antigens in the context of HLA molecules. We hypothesized that T-cells equipped with high affinity CD20-targeting TCRs would be able to recognize B-cell malignancies even in the absence of extracellular CD20...
October 20, 2016: Oncotarget
Katsuhiko Warita, Nana Oshima, Naoko Takeda-Okuda, Jun-Ichi Tamura, Yoshinao Z Hosaka
Chondroitin sulfate (CS), a type of glycosaminoglycan (GAG), is a factor involved in the suppression of myogenic differentiation. CS comprises two repeating sugars and has different subtypes depending on the position and number of bonded sulfate groups. However, the effect of each subtype on myogenic differentiation remains unclear. In this study, we spiked cultures of C₂C12 myoblasts, cells which are capable of undergoing skeletal muscle differentiation, with one of five types of CS (CS-A, -B, -C, -D, or -E) and induced differentiation over a fixed time...
October 21, 2016: Marine Drugs
Meriem Attaf, Stephan J Holland, Istvan Bartok, Julian Dyson
αβ T cells respond to peptide epitopes presented by major histocompatibility complex (MHC) molecules. The role of T cell receptor (TCR) germline complementarity determining regions (CDR1 and 2) in MHC restriction is not well understood. Here, we examine T cell development, MHC restriction and antigen recognition where germline CDR loop structure has been modified by multiple glycine/alanine substitutions. Surprisingly, loss of germline structure increases TCR engagement with MHC ligands leading to excessive loss of immature thymocytes...
October 24, 2016: Scientific Reports
Gil Benedek, Arthur A Vandenbark, Nabil J Alkayed, Halina Offner
The worldwide prevalence of stroke continues to rise despite recent successes in treating acute ischemic stroke. With limited patient eligibility and associated risk of tPA and mechanical thrombectomy, new preventive and therapeutic modalities are needed to stave the rising wave of stroke. Inflammation plays a key role in brain damage after cerebral ischemia, and novel therapies that target pro-inflammatory cells have demonstrated promise for treatment for stroke. Partial MHC class II constructs have been shown to prevent and/or reverse clinical signs of various inflammatory diseases such as experimental autoimmune encephalomyelitis, collagen-induced arthritis and experimental autoimmune uveitis, by reducing the number and frequency of activated cells in the damaged CNS...
October 20, 2016: Neurochemistry International
J Cvetkovic, L Sofronic-Milosavljevicj, N Ilic, M Gnjatovic, I Nagano, A Gruden-Movsesijan
Excretory-secretory antigens (ES L1) of Trichinella spiralis muscle larvae can induce the semi-matured status of rat dendritic cells (DCs). This may at least partly be the consequence of transient activation of extracellular signal-regulated kinases 1/2 (ERK1/2). Here we investigated the potential of several components of ES L1 (native fraction containing 45, 49 and 53 kDa proteins and recombinant Tsp53, representing one of the constituents of this fraction) to demonstrate previously observed effects of ES L1 on DCs in vitro, characterized by establishment of a particular phenotype (very low MHC II expression, moderate CD86 expression and significant ICAM-1 expression) and functional properties (low production of pro-inflammatory cytokine IL-12p70, and high production of IL-10 and TGF-β)...
October 20, 2016: International Journal for Parasitology
Nel Otting, Marit K H van der Wiel, Nanine de Groot, Annemiek J M de Vos-Rouweler, Natasja G de Groot, Gaby G M Doxiadis, Roger W Wiseman, David H O'Connor, Ronald E Bontrop
The human major histocompatibility complex (MHC) region encodes three types of class II molecules designated HLA-DR, -DQ, and -DP. Both the HLA-DQ and -DP gene region comprise a duplicated tandem of A and B genes, whereas in macaques, only one set of genes is present per region. A substantial sequencing project on the DQ and DP genes in various macaque populations resulted in the detection of previously 304 unreported full-length alleles. Phylogenetic studies showed that humans and macaques share trans-species lineages for the DQA1 and DQB1 genes, whereas the DPA1 and DPB1 lineages in macaques appear to be species-specific...
October 22, 2016: Immunogenetics
Denise Mathes, Johannes Weirather, Peter Nordbeck, Anahi-Paula Arias-Loza, Matthias Burkard, Christina Pachel, Thomas Kerkau, Niklas Beyersdorf, Stefan Frantz, Ulrich Hofmann
OBJECTIVE: The present study analyzed the effect of CD4(+) Forkhead box protein 3 negative (Foxp3(-)) T-cells and Foxp3(+) CD4(+) T-cells on infarct size in a mouse myocardial ischemia-reperfusion model. APPROACH AND RESULTS: We examined the infarct size as a fraction of the area-at-risk as primary study endpoint in mice after 30minutes of coronary ligation followed by 24hours of reperfusion. CD4(+) T-cell deficient MHC-II KO mice showed smaller histologically determined infarct size (34...
October 19, 2016: Journal of Molecular and Cellular Cardiology
Shanzheng Lu, Ganggang Shi, Xiaoxi Xu, Grace Wang, Xu Lan, Peng Sun, Xiang Li, Baoren Zhang, Xiangying Gu, Thomas E Ichim, Hao Wang
BACKGROUND: The endometrial regenerative cell (ERC) is a novel type of adult mesenchymal stem cell isolated from menstrual blood. Previous studies demonstrated that ERCs possess unique immunoregulatory properties in vitro and in vivo, as well as the ability to differentiate into functional hepatocyte-like cells. For these reasons, the present study was undertaken to explore the effects of ERCs on carbon tetrachloride (CCl4)-induced acute liver injury (ALI). METHODS: An ALI model in C57BL/6 mice was induced by administration of intraperitoneal injection of CCl4...
October 22, 2016: Journal of Translational Medicine
G Kamkamidze, M Butsashvili, K Gendzekhadze
Hepatitis C virus (HCV) infection remains one of the most important blood-borne diseases worldwide with about 130-170 million people chronically infected with hepatitis C virus, and more than 350 000 people die from hepatitis C-related liver diseases each year. Infection with HCV becomes chronic in approximately 80% of cases, while in up to 20% of cases hepatitis C virus is cleared from the human organism. Chronic infections of hepatitis C often leads to the end-stage liver diseases such as cirrhosis and hepatocellular carcinoma...
September 2016: Georgian Medical News
Xiaodan Luo, Lihua Xu, Yangqiu Li, Huo Tan
Graft-versus-host disease (GVHD) induced by host antigen-presenting cells (APCs) and donor-derived T cells remains the major limitation of allogeneic bone marrow transplantation (allo-BMT). Notch signaling pathway is a highly conserved cell-cell communication that is important in T cell development. Recently, Notch signaling pathway is reported to be involved in regulating GVHD. To investigate the role of Notch inhibition in modulating GVHD, we established MHC-mismatched murine allo-BMT model. We found that inhibition of Notch signaling pathway by γ-secretase inhibitor in vivo could reduce aGVHD, which was shown by the onset time of aGVHD, body weight, clinical aGVHD scores, pathology aGVHD scores, and survival...
October 21, 2016: Cell Biology and Toxicology
Alexis V Mickelson, Sampath K Gollapudi, Murali Chandra
The present study investigated the functional consequences of the human hypertrophic cardiomyopathy (HCM) mutation, A28V, in cardiac troponin T (TnT). The A28V mutation is located within the N-terminus of TnT, a region known to be important for full activation of cardiac thin filaments. The functional consequences of the A28V mutation in TnT remain unknown. Given how α- and β-myosin heavy chain (MHC) isoforms differently alter the effect of the N-terminus of TnT, we hypothesized that the A28V-induced effects would be differently modulated by α- and β-MHC isoforms...
October 21, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Pradipta Ranjan Rauta, Sarbani Ashe, Debasis Nayak, Bismita Nayak
Virulence-related outer membrane proteins (Omps) are expressed in bacteria (Gram-negative) such as V. cholerae and are vital to bacterial invasion in to eukaryotic cell and survival within macrophages that could be best candidate for development of vaccine against V. cholerae. Applying in silico approaches, the 3-D model of the Omp was developed using Swiss model server and validated byProSA and Procheck web server. The continuous stretch of amino acid sequences 26mer: RTRSNSGLLTWGDKQTITLEYGDPAL and 31mer: FFAGGDNNLRGYGYKSISPQDASGALTGAKY having B-cell binding sites were selected from sequence alignment after B cell epitopes prediction by BCPred and AAP prediction modules of BCPreds...
October 12, 2016: Computational Biology and Chemistry
Nadia F Nocera, M Catherine Lee, Lucy M De La Cruz, Cinthia Rosemblit, Brian J Czerniecki
The ErbB/B2 (HER-2/neu) oncogene family plays a critical role in the development and metastatic spread of several tumor types including breast, ovarian and gastric cancer. In breast cancer, HER-2/neu is expressed in early disease development in a large percentage of DCIS lesions and its expression is associated with an increased risk of invasion and recurrence. Targeting HER-2 with antibodies such as trastuzumab or pertuzumab has improved survival, but patients with more extensive disease may develop resistance to therapy...
2016: Frontiers in Pharmacology
Lis N Velásquez, M Ayelén Milillo, M Victoria Delpino, Aldana Trotta, Pablo Fernández, Roberto G Pozner, Roland Lang, Luciana Balboa, Guillermo H Giambartolomei, Paula Barrionuevo
Brucella abortus is an intracellular pathogen capable of surviving inside of macrophages. The success of B. abortus as a chronic pathogen relies on its ability to orchestrate different strategies to evade the adaptive CD4(+) T cell responses that it elicits. Previously, we demonstrated that B. abortus inhibits the IFN-γ-induced surface expression of MHC class II (MHC-II) molecules on human monocytes, and this phenomenon correlated with a reduction in antigen presentation. However, the molecular mechanisms, whereby B...
October 20, 2016: Journal of Leukocyte Biology
Takeshi Kimura, Akihiro Yamashita, Keiichi Ozono, Noriyuki Tsumaki
Articular cartilage damage does not spontaneously heal and could ultimately result in a loss of joint function. Damaged cartilage can be repaired with cell/tissue sources that are transplanted, however, autologous chondrocytes are limited in number as a cell source. Induced pluripotent stem cells (iPSCs) are a relatively new and abundant cell source and can be made from the patient, but at considerable cost. Because cartilage is immunoprivileged tissue, allogeneic cartilages have been transplanted effectively without matching for human leukocyte antigen (HLA), but are difficult to acquire due to scarcity of donors...
October 20, 2016: Tissue Engineering. Part A
A H Mattsson, J V Kringelum, C Garde, M Nielsen
Pan-specific prediction of receptor-ligand interaction is conventionally done using machine-learning methods that integrates information about both receptor and ligand primary sequences. To achieve optimal performance using machine learning, dealing with overfitting and data redundancy is critical. Most often so-called ligand clustering methods have been used to deal with these issues in the context of pan-specific receptor-ligand predictions, and the MHC system the approach has proven highly effective for extrapolating information from a limited set of receptors with well characterized binding motifs, to others with no or very limited experimental characterization...
October 20, 2016: HLA
Aleksandra Biedrzycka, Alvaro Sebastian, Magdalena Migalska, Helena Westerdahl, Jacek Radwan
Characterisation of highly duplicated genes, such as genes of the major histocompatibility complex (MHC), where multiple loci often co-amplify, has until recently been hindered by insufficient read depths per amplicon. Here we used ultra-deep Illumina sequencing to resolve genotypes at exon 3 of MHC class I genes in the sedge warbler (Acrocephalus schoenobaenus). We sequenced 24 individuals in two replicates and used this data, as well as a simulated dataset, to test the effect of amplicon coverage (range: 500-20 000 reads per amplicon) on the repeatability of genotyping using four different genotyping approaches...
October 19, 2016: Molecular Ecology Resources
Srinika Ranasinghe, Pedro A Lamothe, Damien Z Soghoian, Samuel W Kazer, Michael B Cole, Alex K Shalek, Nir Yosef, R Brad Jones, Faith Donaghey, Chioma Nwonu, Priya Jani, Gina M Clayton, Frances Crawford, Janice White, Alana Montoya, Karen Power, Todd M Allen, Hendrik Streeck, Daniel E Kaufmann, Louis J Picker, John W Kappler, Bruce D Walker
CD8(+) T cell recognition of virus-infected cells is characteristically restricted by major histocompatibility complex (MHC) class I, although rare examples of MHC class II restriction have been reported in Cd4-deficient mice and a macaque SIV vaccine trial using a recombinant cytomegalovirus vector. Here, we demonstrate the presence of human leukocyte antigen (HLA) class II-restricted CD8(+) T cell responses with antiviral properties in a small subset of HIV-infected individuals. In these individuals, T cell receptor β (TCRβ) analysis revealed that class II-restricted CD8(+) T cells underwent clonal expansion and mediated killing of HIV-infected cells...
October 18, 2016: Immunity
Stephen A Migueles, Mark Connors
CD8(+) T cells that recognize peptides presented by MHC class II molecules have been observed in a macaque SIV vaccine model. A new study by Ranasinghe et al. (2016) shows that virus-specific class-II-restricted CD8(+) T cells can be found in some HIV-infected patients.
October 18, 2016: Immunity
Yoshie Kametani, Shino Ohshima, Asuka Miyamoto, Atsuko Shigenari, Masaki Takasu, Noriaki Imaeda, Tatsuya Matsubara, Masafumi Tanaka, Takashi Shiina, Hiroshi Kamiguchi, Ryuji Suzuki, Hitoshi Kitagawa, Jerzy K Kulski, Noriaki Hirayama, Hidetoshi Inoko, Asako Ando
The class I major histocompatibility complex (MHC) presents self-developed peptides to specific T cells to induce cytotoxity against infection. The MHC proteins are encoded by multiple loci that express numerous alleles to preserve the variability of the antigen-presenting ability in each species. The mechanism regulating MHC mRNA and protein expression at each locus is difficult to analyze because of the structural and sequence similarities between alleles. In this study, we examined the correlation between the mRNA and surface protein expression of swine leukocyte antigen (SLA)-1*0401 after the stimulation of peripheral blood mononuclear cells (PBMCs) by Staphylococcus aureus superantigen toxic shock syndrome toxin-1 (TSST-1)...
2016: PloS One
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