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https://www.readbyqxmd.com/read/28811364/mechanosensing-drives-acuity-of-%C3%AE-%C3%AE-t-cell-recognition
#1
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
https://www.readbyqxmd.com/read/28811319/galectin-8-activates-dendritic-cells-and-stimulates-antigen-specific-immune-response-elicitation
#2
Julieta Carabelli, Valeria Quattrocchi, Alejandra D'Antuono, Patricia Zamorano, María Virginia Tribulatti, Oscar Campetella
Galectin-8 (Gal-8) is a mammalian β-galactoside-binding lectin, endowed with proinflammatory properties. Given its capacity to enhance antigen-specific immune responses in vivo, we investigated whether Gal-8 was also able to promote APC activation to sustain T cell activation after priming. Both endogenous [dendritic cells (DCs)] and bone marrow-derived DCs (BMDCs) treated with exogenous Gal-8 exhibited a mature phenotype characterized by increased MHC class II (MHCII), CD80, and CD86 surface expression. Moreover, Gal-8-treated BMDCs (Gal-8-BMDCs) stimulated antigen-specific T cells more efficiently than immature BMDCs (iBMDCs)...
August 15, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28803690/new-insights-into-non-conventional-epitopes-as-t-cell-targets-the-missing-link-for-breaking-immune-tolerance-in-autoimmune-disease
#3
REVIEW
James Harbige, Martin Eichmann, Mark Peakman
The mechanism by which immune tolerance is breached in autoimmune disease is poorly understood. One possibility is that post-translational modification of self-antigens leads to peripheral recognition of neo-epitopes against which central and peripheral tolerance is inadequate. Accumulating evidence points to multiple mechanisms through which non-germline encoded sequences can give rise to these non-conventional epitopes which in turn engage the immune system as T cell targets. In particular, where these modifications alter the rules of epitope engagement with MHC molecules, such non-conventional epitopes offer a persuasive explanation for associations between specific HLA alleles and autoimmune diseases...
August 10, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28798348/fas-ligand-mediated-cytotoxicity-of-cd4-t-cells-during-chronic-retrovirus-infection
#4
Anna Malyshkina, Elisabeth Littwitz-Salomon, Kathrin Sutter, Gennadiy Zelinskyy, Sonja Windmann, Simone Schimmer, Annette Paschen, Hendrik Streeck, Kim J Hasenkrug, Ulf Dittmer
CD4+ helper T cells and cytotoxic CD8+ T cells are key players for adaptive immune responses against acute infections with retroviruses. Similar to textbook knowledge the most important function of CD4+ T cells during an acute retrovirus infection seems to be their helper function for other immune cells. Whereas there was no direct anti-viral activity of CD4+ T cells during acute Friend Virus (FV) infection, they were absolutely required for the control of chronic infection. During chronic FV infection a population of activated FV-specific CD4+ T cells did not express cytotoxic molecules, but Fas Ligand that can induce Fas-induced apoptosis in target cells...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28791392/the-mechanism-of-de-novo-expression-of-programmed-cell-death-ligand-1-in-squamous-cell-carcinoma-of-the-lung
#5
Tomoyuki Igarashi, Koji Teramoto, Mitsuaki Ishida, Jun Hanaoka, Yataro Daigo
Immune checkpoint mechanisms such as the programmed cell death-ligand 1-programmed cell death 1 (PD‑L1-PD‑1) axis are utilized by tumor cells to evade the cytotoxicity of effector immune cells. However, environmental factors responsible for the expression of PD‑L1 on tumor cells remain to be fully elucidated. We hypothesized that an immunological interaction with tumor-infiltrating CD8+ lymphocytes (CD8+ TILs) would contribute to PD‑L1 expression in tumor cells. To verify this hypothesis, we examined the effect of interferon-γ (IFN-γ), a cytokine secreted by CD8+ TILs, on PD‑L1 expression in pulmonary squamous cell carcinomas in vitro...
August 3, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28782517/structural-analysis-of-owl-monkey-mhc-dr-shows-that-fully-protective-malaria-vaccine-components-can-be-readily-used-in-humans
#6
Carlos F Suárez, Laura Pabón, Ana Barrera, Jorge Aza-Conde, Manuel Alfonso Patarroyo, Manuel Elkin Patarroyo
More than 50 years ago the owl monkey (genus Aotus) was found to be highly susceptible to developing human malaria, making it an excellent experimental model for this disease. Microbes and parasites' (especially malaria) tremendous genetic variability became resolved during our malaria vaccine development, involving conserved peptides having high host cell binding activity (cHABPs); however, cHABPs are immunologically silent and must be specially modified (mHABPs) to induce a perfect fit into major histocompatibility complex (MHC) molecules (HLA in humans)...
August 3, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28767728/crystal-structure-of-qa-1a-with-bound-qa-1-determinant-modifier-peptide
#7
Ge Ying, Jing Wang, Vipin Kumar, Dirk M Zajonc
Qa-1 is a non-classical Major Histocompatibility (MHC) class I molecule that generally presents hydrophobic peptides including Qdm derived from the leader sequence of classical MHC I molecules for immune surveillance by NK cells. Qa-1 bound peptides derived from the TCR Vβ8.2 of activated T cells also activates CD8+ regulatory T cells to control autoimmunity and maintain self-tolerance. Four allotypes of Qa-1 (Qa-1a-d) are expressed that are highly conserved in sequence but have several variations that could affect peptide binding to Qa-1 or TCR recognition...
2017: PloS One
https://www.readbyqxmd.com/read/28767693/dendritic-cells-that-phagocytose-apoptotic-macrophages-loaded-with-mycobacterial-antigens-activate-cd8-t-cells-via-cross-presentation
#8
Patricia Espinosa-Cueto, Alejandro Magallanes-Puebla, Carlos Castellanos, Raul Mancilla
While homeostatic apoptosis is immunologically silent, macrophage apoptosis during Mycobacterium tuberculosis infection can potentially induce an immune response against the mycobacteria. To examine the role of dendritic cells in this response, macrophage apoptosis was induced by incubating the macrophage with cell wall extracts of mycobacteria expressing LpqH. The apoptogenic proteins of the cell wall extracts were engulfed by the macrophage and then were translocated from the cytosol to the nuclei of the dying cells...
2017: PloS One
https://www.readbyqxmd.com/read/28759565/low-doses-of-cholera-toxin-and-its-mediator-camp-induce-ctla-2-secretion-by-dendritic-cells-to-enhance-regulatory-t-cell-conversion
#9
Cinthia Silva-Vilches, Katrien Pletinckx, Miriam Lohnert, Vladimir Pavlovic, Diyaaeldin Ashour, Vini John, Emilia Vendelova, Susanne Kneitz, Jie Zhou, Rena Chen, Thomas Reinheckel, Thomas D Mueller, Jochen Bodem, Manfred B Lutz
Immature or semi-mature dendritic cells (DCs) represent tolerogenic maturation stages that can convert naive T cells into Foxp3+ induced regulatory T cells (iTreg). Here we found that murine bone marrow-derived DCs (BM-DCs) treated with cholera toxin (CT) matured by up-regulating MHC-II and costimulatory molecules using either high or low doses of CT (CThi, CTlo) or with cAMP, a known mediator CT signals. However, all three conditions also induced mRNA of both isoforms of the tolerogenic molecule cytotoxic T lymphocyte antigen 2 (CTLA-2α and CTLA-2β)...
2017: PloS One
https://www.readbyqxmd.com/read/28759104/the-interplay-between-hla-b27-and-erap1-erap2-aminopeptidases-from-antiviral-protection-to-spondyloarthritis
#10
REVIEW
Carolina Vitulano, Valentina Tedeschi, Fabiana Paladini, Rosa Sorrentino, Maria Teresa Fiorillo
The human leukocyte antigen class I gene HLA-B27 is the strongest risk factor for Ankylosing Spondylitis (AS), a chronic inflammatory arthritic disorder. More recently, the Endoplasmic Reticulum Aminopeptidases (ERAP) 1 and 2 genes have been identified by genome-wide association studies (GWAS) as additional susceptibility factors. In the ER, these aminopeptidases trim the peptides to a length suitable to fit into the groove of the MHC class I molecules. Noteworthy, an epistatic interaction between HLA-B27 and ERAP1, but not between HLA-B27 and ERAP2, has been highlighted...
July 31, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28756915/in-silico-identification-and-characterization-of-common-epitope-based-peptide-vaccine-for-nipah-and-hendra-viruses
#11
Chayan Kumar Saha, Md Mahbub Hasan, Md Saddam Hossain, Md Asraful Jahan, Abul Kalam Azad
OBJECTIVE: To explore a common B- and T-cell epitope-based vaccine that can elicit an immune response against encephalitis causing genus Henipaviruses, Hendra virus (HeV) and Nipah virus (NiV). METHODS: Membrane proteins F, G and M of HeV and NiV were retrieved from the protein database and subjected to different bioinformatics tools to predict antigenic B-cell epitopes. Best B-cell epitopes were then analyzed to predict their T-cell antigenic potentiality. Antigenic B- and T-cell epitopes that shared maximum identity with HeV and NiV were selected...
June 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/28755382/tools-to-define-the-melanoma-associated-immunopeptidome
#12
REVIEW
Eva Bräunlein, Angela M Krackhardt
Immunotherapies have been traditionally applied in malignant melanoma representing one of the most immunogenic tumors at all. Recently, immune checkpoint modulation has shown high therapeutic efficacy and may provide long-term survival in a significant proportion of affected patients. T cells are the major players in tumor rejection and recognize tumor cells predominantly in a major histocompatibility complex (MHC)-dependent way. The immunopeptidome comprises the peptide repertoire presented by MHC class I and II molecules on the surface of the body's cells including tumor cells...
July 29, 2017: Immunology
https://www.readbyqxmd.com/read/28751109/polymorphism-and-peptide-binding-specificities-of-porcine-major-histocompatibility-complex-mhc-class-i-molecules
#13
Shuhua Fan, Yongli Wang, Song Wang, Xian Wang, Yanan Wu, Zibin Li, Nianzhi Zhang, Chun Xia
The swine lymphocyte antigen class I (SLA I) is a highly polymorphic gene superfamily that plays an important role in swine anti-viral immune responses. However, an understanding of the highly variable sites and peptide-binding specificities of SLA I molecule is limited. In this study, a total of 27 SLA I alleles were identified from 3 Tibetan wild boars and 3 Heishan pigs. The phylogenetic relationship between the Tibetan wild boar and other breeds was analyzed using bioinformatics methods, and the highly variable sites were noted in the three dimensional structures of SLA I...
July 24, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28747978/comparative-study-of-the-immunological-characteristics-of-three-different-c57bl-6n-mouse-substrains
#14
Jun Young Choi, Hye Ryeong Kim, Kil Soo Kim, Young-Suk Jung, Joon Young Cho, Dae Youn Hwang, Hyun Keun Song
Inbred mice, a systematically developed homogeneous animal, have been developed to maintain experimental reproducibility and to minimize experimental variables in animal-based studies. In particular, C57BL/6 mice are frequently used in experiments into immunology and antitumor activity experiments. This study was compared the immunological characteristics of C57BL/6NKorl, a Korean developed experimental animal resource, with those of two other C57BL/6N substrains. Mouse body, thymus, and spleen weights in C57BL/6NKorl were not significantly different from those of the other two C57BL/6N substrains...
June 2017: Laboratory Animal Research
https://www.readbyqxmd.com/read/28740497/the-role-of-multiscale-protein-dynamics-in-antigen-presentation-and-t-lymphocyte-recognition
#15
R Charlotte Eccleston, Shunzhou Wan, Neil Dalchau, Peter V Coveney
T lymphocytes are stimulated when they recognize short peptides bound to class I proteins of the major histocompatibility complex (MHC) protein, as peptide-MHC complexes. Due to the diversity in T-cell receptor (TCR) molecules together with both the peptides and MHC proteins they bind to, it has been difficult to design vaccines and treatments based on these interactions. Machine learning has made some progress in trying to predict the immunogenicity of peptide sequences in the context of specific MHC class I alleles but, as such approaches cannot integrate temporal information and lack explanatory power, their scope will always be limited...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28740080/a-new-marine-derived-sulfoglycolipid-triggers-dendritic-cell-activation-and-immune-adjuvant-response
#16
Emiliano Manzo, Adele Cutignano, Dario Pagano, Carmela Gallo, Giusi Barra, Genoveffa Nuzzo, Clementina Sansone, Adrianna Ianora, Konrad Urbanek, Daniela Fenoglio, Francesca Ferrera, Cinzia Bernardi, Alessia Parodi, Giuseppe Pasquale, Antonio Leonardi, Gilberto Filaci, Raffaele De Palma, Angelo Fontana
Dendritic Cells (DCs) recognize infectious non-self molecules and engage the adaptive immune system thereby initiating long lasting, antigen-specific responses. As such, the ability to activate DCs is considered a key tool to enhance the efficacy and quality of vaccination. Here we report a novel immunomodulatory sulfolipid named β-SQDG18 that prototypes a class of natural-derived glycolipids able to prime human DCs by a TLR2/TLR4-independent mechanism and trigger an efficient immune response in vivo. β-SQDG18 induces maturation of DC with the upregulation of MHC II molecules and co-stimulatory proteins (CD83, CD86), as well as pro-inflammatory cytokines (IL-12 and INF-γ)...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28738674/complex-consisting-of-%C3%AE-glucan-and-antigenic-peptides-with-cleavage-site-for-glutathione-and-aminopeptidases-induces-potent-cytotoxic-t-lymphocytes
#17
Shinichi Mochizuki, Hiromi Morishita, Kazuo Sakurai
The efficient induction of antigen-specific immune responses requires not only promotion of the uptake of antigens and adjuvant molecules into antigen-presenting cells, but also control of their intracellular behavior. We previously demonstrated that the β-glucan schizophyllan (SPG) can form complexes with CpG oligonucleotides with attached dA40 (CpG-dA/SPG), which can accumulate in macrophages in the draining inguinal lymph nodes and induce strong immune responses. In this study, we prepared various conjugates comprising antigenic peptide (OVA257-264) and dA40, and made complexes with SPG...
July 24, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28733878/role-of-tgf-%C3%AE-in-self-peptide-regulation-of-autoimmunity
#18
REVIEW
Bhagirath Singh, Michael D Krawetz, Rachel M De Lima, Rinee Mukherjee, Pratibha Chaturvedi, Edwin Lee-Chan, Edward H Leiter, Kelly L Summers
Transforming growth factor (TGF)-β has been implicated in regulation of the immune system, including autoimmunity. We have found that TGF-β is readily produced by T cells following immunization with self-peptide epitopes that downregulate autoimmune responses in type 1 diabetes (T1D) prone nonobese diabetic (NOD) mice. These include multiple peptide epitopes derived from the islet β-cell antigens GAD65 (GAD65 p202-221, GAD65 p217-236), GAD67 (GAD67 p210-229, GAD67 p225-244), IGRP (IGRP p123-145, IGRP p195-214) and insulin B-chain (Ins...
July 21, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28723951/cd8-t-cells-provide-immune-protection-against-murine-disseminated-endotheliotropic-orientia-tsutsugamushi-infection
#19
Guang Xu, Nicole L Mendell, Yuejin Liang, Thomas R Shelite, Yenny Goez-Rivillas, Lynn Soong, Donald H Bouyer, David H Walker
Scrub typhus, caused by a Gram-negative obligately intracellular coccobacillus, Orientia tsutsugamushi, is a long neglected but important tropical disease. Orientia tsutsugamushi causes illness in one million people each year, and 1 billion people are at risk. Without appropriate diagnosis and treatment, the disease can cause severe multiorgan failure with a case fatality rate of 7-15%. The current gaps in knowledge of immunity include the unknown mechanisms of host immunity to O. tsutsugamushi. Using an intravenous (i...
July 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28720143/mhc-class-ii-expression-and-potential-antigen-presenting-cells-in-the-retina-during-experimental-autoimmune-uveitis
#20
Deborah A Lipski, Rémi Dewispelaere, Vincent Foucart, Laure E Caspers, Matthieu Defrance, Catherine Bruyns, François Willermain
BACKGROUND: Controversy exists regarding which cell types are responsible for autoantigen presentation in the retina during experimental autoimmune uveitis (EAU) development. In this study, we aimed to identify and characterize the retinal resident and infiltrating cells susceptible to express major histocompatibility complex (MHC) class II during EAU. METHODS: EAU was induced in C57BL/6 mice by adoptive transfer of autoreactive lymphocytes from IRBP1-20-immunized animals...
July 18, 2017: Journal of Neuroinflammation
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