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Immunodominant T cell

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https://www.readbyqxmd.com/read/28618262/the-helper-t-cell-s-dilemma-in-tuberculosis
#1
Daniel L Barber
Vaccination approaches eliciting strong CD4 T cell responses provide only weak protection from tuberculosis. In this issue of Cell Host & Microbe, Moguche et al. (2017) show that T cells specific for different immunodominant vaccine antigens can fail to protect for opposite reasons, highlighting a major challenge in tuberculosis vaccine design.
June 14, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28600217/limited-genetic-diversity-in-the-global-plasmodium-vivax-cell-traversal-protein-of-ookinetes-and-sporozoites-celtos-sequences-implications-for-pvceltos-based-vaccine-development
#2
Akram Abouie Mehrizi, Fatemeh Torabi, Sedigheh Zakeri, Navid Dinparast Djadid
Cell traversal protein of Ookinetes and Sporozoites (CelTOS) is a new malaria vaccine candidate antigen. Since one of the main challenges in malaria vaccine development is the extensive antigenic diversity of this parasite, local and global gene diversity analysis is of particular importance. Therefore, in this study, the genetic diversity of pvceltos gene was investigated among Iranian P. vivax isolates (n=46) and compared with available worldwide pvceltos sequences. One synonymous (C109A) and three amino acid replacements (V118L, K178T, and G179R) were observed in Iranian pvceltos sequences in compare with Sal-1 sequence leading to five haplotypes including PvCelt-A (GSVKGL, 13%), PvCelt-B (GSLKGL, 50%), PvCelt-C (GSLTGL, 17...
June 6, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28597552/branched-chain-%C3%AE-ketoacid-dehydrogenase-kinase-111-130-a-t-cell-epitope-that-induces-both-autoimmune-myocarditis-and-hepatitis-in-a-j-mice
#3
Bharathi Krishnan, Chandirasegaran Massilamany, Rakesh H Basavalingappa, Arunakumar Gangaplara, Guobin Kang, Qingsheng Li, Francisco A Uzal, Jennifer L Strande, Gustavo A Delhon, Jean-Jack Riethoven, David Steffen, Jay Reddy
INTRODUCTION: Organ-specific autoimmune diseases are believed to result from immune responses generated against self-antigens specific to each organ. However, when such responses target antigens expressed promiscuously in multiple tissues, then the immune-mediated damage may be wide spread. METHODS: In this report, we describe a mitochondrial protein, branched chain α-ketoacid dehydrogenase kinase (BCKDk ) that can act as a target autoantigen in the development of autoimmune inflammatory reactions in both heart and liver...
June 9, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28594344/design-and-synthesis-of-non-peptide-mimetics-mapping-the-immunodominant-myelin-basic-protein-mbp83-96-epitope-to-function-as-t-cell-receptor-antagonists
#4
Mary-Patricia Yannakakis, Carmen Simal, Haralambos Tzoupis, Maria Rodi, Narges Dargahi, Monica Prakash, Athanasia Mouzaki, James A Platts, Vasso Apostolopoulos, Theodore V Tselios
Encephalitogenic T cells are heavily implicated in the pathogenesis of multiple sclerosis (MS), an autoimmune demyelinating disease of the central nervous system. Their stimulation is triggered by the formation of a trimolecular complex between the human leukocyte antigen (HLA), an immunodominant myelin basic protein (MBP) epitope, and the T cell receptor (TCR). We detail herein our studies directed towards the rational design and synthesis of non-peptide mimetic molecules, based on the immunodominant MBP83-96 epitope that is recognized by the TCR in complex with HLA...
June 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28592428/ebv-infection-empowers-human-b-cells-for-autoimmunity-role-of-autophagy-and-relevance-to-multiple-sclerosis
#5
Elena Morandi, S Anwar Jagessar, Bert A 't Hart, Bruno Gran
The efficacy of B cell depletion therapy in multiple sclerosis indicates their central pathogenic role in disease pathogenesis. The B lymphotropic EBV is a major risk factor in multiple sclerosis, via as yet unclear mechanisms. We reported in a nonhuman primate experimental autoimmune encephalomyelitis model that an EBV-related lymphocryptovirus enables B cells to protect a proteolysis-sensitive immunodominant myelin oligodendrocyte glycoprotein (MOG) epitope (residues 40-48) against destructive processing...
June 7, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28588287/identification-and-evaluation-of-the-novel-immunodominant-antigen-rv2351c-from-mycobacterium-tuberculosis
#6
Xuezhi Wang, Shuangshuang Chen, Yongjuan Xu, Huajun Zheng, Tongyang Xiao, Yuqing Li, Xing Chen, Mingxiang Huang, Haifeng Zhang, Xijing Fang, Yi Jiang, Machao Li, Haican Liu, Kanglin Wan
There is an urgent need for new immunodominant antigens to improve the diagnosis of tuberculosis (TB) and the efficacy of the TB vaccine to control the disease worldwide. In this study, we evaluated the diagnostic potential of a novel Mycobacterium tuberculosis (MTB)-specific antigen, Rv2351c, from region of difference (RD) 7 of the MTB genome, and investigated the potency of the vaccine by identifying its immunological function in human and animal immunological experiments. Twenty T-cell epitopes were identified using TEpredict and prediction tools from the Immune Epitope Database and Analysis Resource...
June 7, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28588103/mycobacteriumtuberculosis-rv3615c-is-a-highly-immunodominant-antigen-and-specifically-inducespotent-th1-type-immune-responses-in-tuberculosis-pleurisy
#7
Jiangping Li, Juan Shen, Suihua Lao, Xiaomin Li, Jie Liu, Changyou Wu
T-cell responses have been demonstrated essential for preventing M.tb infection. The Th1-cytokines produced by T cells, such as INF-γ, IL-2 and TNF-α, not only limit the invasion of M.tb but also eliminate the pathogen at site of infection. BCG is known to induce Th1-type responses but the protection is inadequate. Identification of immunogenic components in addition to those expressed in BCG and induction of a broad spectrum of Th1-type responses provide options for generating sufficient adaptive immunity...
June 6, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28584988/methodology-for-anti-cryptococcal-vaccine-development
#8
Ashok K Chaturvedi, Floyd L Wormley
Cryptococcus neoformans and Cryptococcus gattii, the predominant etiological agents of cryptococcosis, are fungal pathogens that cause disease ranging from a mild pneumonia to life-threatening infections of the central nervous system (CNS). C. neoformans is widely considered an opportunistic fungal pathogen which targets individuals with impaired immune systems, while C. gattii is predominantly associated with fungal infections in immunocompetent individuals. However, C. neoformans and C. gattii have certainly been identified as the causative agent of cryptococcosis in both immune compromised and immune competent individuals...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28583308/an-epitope-specific-derg-pg70-leaps-vaccine-modulates-t-cell-responses-and-suppresses-arthritis-progression-in-two-related-murine-models-of-rheumatoid-arthritis
#9
Katalin Mikecz, Tibor T Glant, Adrienn Markovics, Kenneth S Rosenthal, Julia Kurko, Roy E Carambula, Steve Cress, Harold L Steiner, Daniel H Zimmerman
Rheumatoid arthritis (RA) is an autoimmune joint disease maintained by aberrant immune responses involving CD4+ T helper (Th)1 and Th17 cells. In this study, we tested the therapeutic efficacy of Ligand Epitope Antigen Presentation System (LEAPS™) vaccines in two Th1 cell-driven mouse models of RA, cartilage proteoglycan (PG)-induced arthritis (PGIA) and PG G1-domain-induced arthritis (GIA). The immunodominant PG peptide PG70 was attached to a DerG or J immune cell binding peptide, and the DerG-PG70 and J-PG70 LEAPS vaccines were administered to the mice after the onset of PGIA or GIA symptoms...
June 2, 2017: Vaccine
https://www.readbyqxmd.com/read/28566371/single-cell-rna-sequencing-reveals-expanded-clones-of-islet-antigen-reactive-cd4-t-cells-in-peripheral-blood-of-subjects-with-type-1-diabetes
#10
Karen Cerosaletti, Fariba Barahmand-Pour-Whitman, Junbao Yang, Hannah A DeBerg, Matthew J Dufort, Sara A Murray, Elisabeth Israelsson, Cate Speake, Vivian H Gersuk, James A Eddy, Helena Reijonen, Carla J Greenbaum, William W Kwok, Erik Wambre, Martin Prlic, Raphael Gottardo, Gerald T Nepom, Peter S Linsley
The significance of islet Ag-reactive T cells found in peripheral blood of type 1 diabetes (T1D) subjects is unclear, partly because similar cells are also found in healthy control (HC) subjects. We hypothesized that key disease-associated cells would show evidence of prior Ag exposure, inferred from expanded TCR clonotypes, and essential phenotypic properties in their transcriptomes. To test this, we developed single-cell RNA sequencing procedures for identifying TCR clonotypes and transcript phenotypes in individual T cells...
May 31, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28562659/na%C3%A3-ve-helper-t-cells-with-high-cd5-expression-have-increased-calcium-signaling
#11
Claudia M Tellez Freitas, Garrett J Hamblin, Carlee M Raymond, K Scott Weber
The adaptive immune response is orchestrated by T helper cells and their function is dependent upon interactions between the T cell receptor (TCR), peptide MHC (pMHC) and co-receptors. TCR-pMHC interactions initiate calcium signaling cascades which determine T cell activation, survival, proliferation and differentiation. CD5 is a co-receptor that plays an important role in regulating T cell signaling and fate during thymocyte education. CD5 surface expression on mature single positive thymocytes correlates with the TCR signal strength for positive selecting self-ligands...
2017: PloS One
https://www.readbyqxmd.com/read/28540499/cell-based-therapies-with-t-regulatory-cells
#12
REVIEW
Mateusz Gliwiński, Dorota Iwaszkiewicz-Grześ, Piotr Trzonkowski
CD4(+)CD25(high)FoxP3(+) T regulatory cells (Tregs) are immunodominant suppressors in the immune system. Tregs use various mechanisms to control immune responses. Preclinical data from animal models have confirmed the huge therapeutic potential of Tregs in many immune-mediated diseases. Hence, these cells are now on the road to translation to cell therapy in the clinic as the first clinical trials are accomplished. To date, clinical research has involved mainly hematopoietic stem cell transplantations, solid organ transplantations, and autoimmunity...
May 24, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/28508576/mhc-i-presentation-of-toxoplasma-gondii-immunodominant-antigen-does-not-require-sec-22b-and-is-regulated-by-antigen-orientation-at-the-vacuole-membrane
#13
Célia Buaillon, Nestor A Guerrero, Ignacio Cebrian, Sophie Blanié, Jodie Lopez, Emilie Bassot, Virginie Vasseur, Julien Santi-Rocca, Nicolas Blanchard
The intracellular Toxoplasma gondii parasite replicates within a parasitophorous vacuole (PV). T. gondii secretes proteins that remain soluble in the PV space, are inserted into PV membranes or are exported beyond the PV boundary. In addition to supporting T. gondii growth, these proteins can be processed and presented by MHC I for CD8(+) T-cell recognition. Yet it is unclear whether membrane binding influences the processing pathways employed and if topology of membrane antigens impacts their MHC I presentation...
May 15, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28506538/epitope-specific-immunotherapy-targeting-cd4-positive-t-cells-in-coeliac-disease-two-randomised-double-blind-placebo-controlled-phase-1-studies
#14
Gautam Goel, Tim King, A James Daveson, Jane M Andrews, Janakan Krishnarajah, Richard Krause, Gregor J E Brown, Ronald Fogel, Charles F Barish, Roger Epstein, Timothy P Kinney, Philip B Miner, Jason A Tye-Din, Adam Girardin, Juha Taavela, Alina Popp, John Sidney, Markku Mäki, Kaela E Goldstein, Patrick H Griffin, Suyue Wang, John L Dzuris, Leslie J Williams, Alessandro Sette, Ramnik J Xavier, Ludvig M Sollid, Bana Jabri, Robert P Anderson
BACKGROUND: A gluten-free diet is the only means to manage coeliac disease, a permanent immune intolerance to gluten. We developed a therapeutic vaccine, Nexvax2, designed to treat coeliac disease. Nexvax2 is an adjuvant-free mix of three peptides that include immunodominant epitopes for gluten-specific CD4-positive T cells. The vaccine is intended to engage and render gluten-specific CD4-positive T cells unresponsive to further antigenic stimulation. We assessed the safety and pharmacodynamics of the vaccine in patients with coeliac disease on a gluten-free diet...
May 11, 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28490594/dok-1-and-dok-2-are-required-to-maintain-herpes-simplex-virus-1-specific-cd8-t-cells-in-a-murine-model-of-ocular-infection
#15
Soumia Lahmidi, Mitra Yousefi, Slimane Dridi, Pascale Duplay, Angela Pearson
Dok-1 and Dok-2 negatively regulate responses downstream of several immune receptors in lymphoid and myeloid cells. Recent evidence showed that Dok proteins are essential in the formation of memory CD8(+) T cells to an exogenous epitope expressed by vaccinia virus; however, the importance of Dok-1 and Dok-2 in the control of viral infection is unknown. Herein, we investigated the role of Dok proteins in modulating the immune response against herpes simplex virus 1 (HSV-1) in a mouse model of ocular infection...
May 10, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28467828/dominant-protection-from-hla-linked-autoimmunity-by-antigen-specific-regulatory-t-cells
#16
Joshua D Ooi, Jan Petersen, Yu H Tan, Megan Huynh, Zoe J Willett, Sri H Ramarathinam, Peter J Eggenhuizen, Khai L Loh, Katherine A Watson, Poh Y Gan, Maliha A Alikhan, Nadine L Dudek, Andreas Handel, Billy G Hudson, Lars Fugger, David A Power, Stephen G Holt, P Toby Coates, Jon W Gregersen, Anthony W Purcell, Stephen R Holdsworth, Nicole L La Gruta, Hugh H Reid, Jamie Rossjohn, A Richard Kitching
Susceptibility and protection against human autoimmune diseases, including type I diabetes, multiple sclerosis, and Goodpasture disease, is associated with particular human leukocyte antigen (HLA) alleles. However, the mechanisms underpinning such HLA-mediated effects on self-tolerance remain unclear. Here we investigate the molecular mechanism of Goodpasture disease, an HLA-linked autoimmune renal disorder characterized by an immunodominant CD4(+) T-cell self-epitope derived from the α3 chain of type IV collagen (α3135-145)...
May 11, 2017: Nature
https://www.readbyqxmd.com/read/28467721/reactive-oxygen-species-regulate-both-priming-and-established-arthritis-but-with-different-mechanisms
#17
Outi Sareila, Cecilia Hagert, Tiina Kelkka, Marjo Linja, Bingze Xu, Jan Kihlberg, Rikard Holmdahl
AIMS: Neutrophil cytosolic factor 1 (NCF1) is a key regulatory component of the phagocytic NOX2 complex, which produces reactive oxygen species (ROS). Polymorphism of the Ncf1 gene is associated with increased arthritis severity. In this study, we generated targeted Ncf1 knock-in mice with inducible Ncf1 expression and determined the critical time window during which the NOX2-derived ROS protect the mice from arthritis. RESULTS: Targeted Ncf1 knock-in mice lacked NOX2-derived ROS, and in vivo allelic conversion of Ncf1 by the CreER(T2) recombinase led to full protein expression and ROS production within 10 days...
June 1, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28448594/novel-in-natural-infection-subdominant-hiv-1-cd8-t-cell-epitopes-revealed-in-human-recipients-of-conserved-region-t-cell-vaccines
#18
Nicola Borthwick, Zhansong Lin, Tomohiro Akahoshi, Anuska Llano, Sandra Silva-Arrieta, Tina Ahmed, Lucy Dorrell, Christian Brander, Hayato Murakoshi, Masafumi Takiguchi, Tomáš Hanke
BACKGROUND: Fine definition of targeted CD8+ T-cell epitopes and their human leucocyte antigen (HLA) class I restriction informs iterative improvements of HIV-1 T-cell vaccine designs and may predict early vaccine success or failure. Here, lymphocytes from volunteers, who had received candidate HIVconsv vaccines expressing conserved sub-protein regions of HIV-1, were used to define the optimum-length target epitopes and their HLA restriction. In HIV-1-positive patients, CD8+ T-cell responses predominantly recognize immunodominant, but hypervariable and therefore less protective epitopes...
2017: PloS One
https://www.readbyqxmd.com/read/28446674/broadening-cd4-and-cd8-t-cell-responses-against-hepatitis-c-virus-by-vaccination-with-ns3-overlapping-peptide-panels-in-cross-priming-liposomes
#19
Jonathan Filskov, Marianne Mikkelsen, Paul R Hansen, Jan P Christensen, Allan R Thomsen, Peter Andersen, Jens Bukh, Else Marie Agger
Despite the introduction of effective drugs to treat patients with chronic hepatitis C virus (HCV) infection, a vaccine would be the only means to substantially reduce the worldwide disease burden. An incomplete understanding of how HCV interacts with its human host and evades immune surveillance has hampered vaccine development. It is generally accepted that in infected individuals, a narrow repertoire of exhausted T cells is a hallmark of persistent infection, whereas broad vigorous CD4(+) and CD8(+) T cell responses are associated with control of acute hepatitis C...
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28435676/understanding-cd8-t-cell-responses-toward-the-native-and-alternate-hla-a-02-01-restricted-wt1-epitope
#20
Thi Ho Nguyen, Amabel Cl Tan, Sue D Xiang, Anne Goubier, Kim L Harland, E Bridie Clemens, Magdalena Plebanski, Katherine Kedzierska
The Wilms' tumor 1 (WT1) antigen is expressed in solid and hematological malignancies, but not healthy tissues, making it a promising target for cancer immunotherapies. Immunodominant WT1 epitopes, the native HLA-A2/WT1126-134 (RMFPNAPYL) (HLA-A2/RMFPNAPYL epitope (WT1A)) and its modified variant YMFPNAPYL (HLA-A2/YMFPNAPYL epitope (WT1B)), can induce WT1-specific CD8(+) T cells, although WT1B is more stably bound to HLA-A*02:01. Here, to further determine the benefits of those two targets, we assessed the naive precursor frequencies; immunogenicity and cross-reactivity of CD8(+) T cells directed toward these two WT1 epitopes...
March 2017: Clinical & Translational Immunology
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