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Immunodominant T cell

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https://www.readbyqxmd.com/read/28218747/mhc-i-peptides-get-out-of-the-groove-and-enable-a-novel-mechanism-of-hiv-1-escape
#1
Phillip Pymm, Patricia T Illing, Sri H Ramarathinam, Geraldine M O'Connor, Victoria A Hughes, Corinne Hitchen, David A Price, Bosco K Ho, Daniel W McVicar, Andrew G Brooks, Anthony W Purcell, Jamie Rossjohn, Julian P Vivian
Major histocompatibility complex class I (MHC-I) molecules play a crucial role in immunity by capturing peptides for presentation to T cells and natural killer (NK) cells. The peptide termini are tethered within the MHC-I antigen-binding groove, but it is unknown whether other presentation modes occur. Here we show that 20% of the HLA-B*57:01 peptide repertoire comprises N-terminally extended sets characterized by a common motif at position 1 (P1) to P2. Structures of HLA-B*57:01 presenting N-terminally extended peptides, including the immunodominant HIV-1 Gag epitope TW10 (TSTLQEQIGW), showed that the N terminus protrudes from the peptide-binding groove...
February 20, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28212503/lactobacillus-buchneri-s-layer-as-carrier-for-an-ara-h-2-derived-peptide-for-peanut-allergen-specific-immunotherapy
#2
Julia Anzengruber, Merima Bublin, Eva Bönisch, Bettina Janesch, Angelika Tscheppe, Matthias L Braun, Eva-Maria Varga, Christine Hafner, Heimo Breiteneder, Christina Schäffer
Peanut allergy is an IgE-mediated severe hypersensitivity disorder. The lack of a treatment of this potentially fatal allergy has led to intensive research on vaccine development. Here, we describe the design and initial characterization of a carrier-bound peptide derived from the most potent peanut allergen, Ara h 2, as a candidate vaccine. Based on the adjuvant capability of bacterial surface (S-) layers, a fusion protein of the S-layer protein SlpB from Lactobacillus buchneri CD034 and the Ara h 2-derived peptide AH3a42 was produced...
February 14, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28194152/hsp65-producing-lactococcus-lactis-prevents-inflammatory-intestinal-disease-in-mice-by-il-10-and-tlr2-dependent-pathways
#3
Ana Cristina Gomes-Santos, Rafael Pires de Oliveira, Thaís Garcias Moreira, Archimedes Barbosa Castro-Junior, Bernardo Coelho Horta, Luísa Lemos, Leonardo Augusto de Almeida, Rafael Machado Rezende, Denise Carmona Cara, Sérgio Costa Oliveira, Vasco Ariston Carvalho Azevedo, Anderson Miyoshi, Ana Maria Caetano Faria
Heat shock proteins (Hsps) are highly expressed at all sites of inflammation. As they are ubiquitous and immunodominant antigens, these molecules represent good candidates for the therapeutic use of oral tolerance in autoimmune and chronic inflammatory diseases. Evidences from human and animal studies indicate that inflammatory bowel disease (IBD) results from uncontrolled inflammatory responses to intestinal microbiota. Hsps are immunodominant proteins expressed by several immune cells and by commensal bacteria...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28188174/brain-atrophy-in-picornavirus-infected-fvb-mice-is-dependent-on-the-h-2d-b-class-i-molecule
#4
April M Huseby Kelcher, Pascal A Atanga, Jeffrey D Gamez, Luz M Cumba Garcia, Stephanie J Teclaw, Kevin D Pavelko, Slobodan I Macura, Aaron J Johnson
Brain atrophy is a common feature of numerous neurologic diseases in which the role of neuroinflammation remains ill-defined. In this study, we evaluated the contribution of major histocompatibility complex class I molecules to brain atrophy in Theiler's murine encephalomyelitis virus (TMEV)-infected transgenic FVB mice that express the D(b) class I molecule. FVB/D(b) and wild-type FVB mice were evaluated for changes in neuroinflammation, virus clearance, neuropathology, and development of brain atrophy via T2-weighted MRI and subsequent 3-dimensional volumetric analysis...
February 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28178428/effect-of-histophilus-somni-on-heart-and-brain-microvascular-endothelial-cells
#5
D O'Toole, R Hunter, T Allen, B Zekarias, J Lehmann, K S Kim, D Grab, L B Corbeil
Histophilus somni is a pathogenic gram-negative bacterium responsible for pneumonia and septicemia in cattle. Sequelae include infectious thrombotic meningoencephalitis (ITME), myocarditis, arthritis, and abortion. These syndromes are associated with widespread vasculitis and thrombosis, implicating a role for endothelium in pathogenesis. Histopathologic and immunohistochemical investigation of 10 natural cases of bovine H. somni myocarditis and 1 case of ITME revealed intravascular H. somni in large biofilm-like aggregates adherent to the luminal surface of microvascular endothelium...
January 1, 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/28148910/intein-mediated-backbone-cyclization-of-vp1-protein-enhanced-protection-of-cvb3-induced-viral-myocarditis
#6
Xingmei Qi, Sidong Xiong
CVB3 is a common human pathogen to be highly lethal to newborns and causes viral myocarditis and pancreatitis in adults. However, there is no vaccine available for clinical use. CVB3 capsid protein VP1 is an immunodominant structural protein, containing several B- and T-cell epitopes. However, immunization of mice with VP1 protein is ineffective. Cyclization of peptide is commonly used to improve their in vivo stability and biological activity. Here, we designed and synthesizd cyclic VP1 protein by using engineered split Rma DnaB intein and the cyclization efficiency was 100% in E...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28148797/patterns-of-cellular-immunity-associated-with-experimental-infection-with-rden2%C3%AE-30-tonga-74-supports-its-suitability-as-a-human-denv-challenge-strain
#7
Alba Grifoni, Michael Angelo, John Sidney, Sinu Paul, Bjoern Peters, Aruna D de Silva, Elizabeth Phillips, Simon Mallal, Sean A Diehl, Jason Botten, Jonathan Boyson, Beth D Kirkpatrick, Stephen S Whitehead, Anna P Durbin, Alessandro Sette, Daniela Weiskopf
: A deletion variant of the DENV2 Tonga/74 strain lacking 30 nucleotides from its 3' untranslated region (rDEN2Δ30) has previously been established for use in a controlled DENV human challenge model. To evaluate if this model is appropriate to derive correlates of protection for DENV vaccines based on cellular immunity, we wanted to compare how the cellular immune response to this challenge strain compares to the response induced by natural infection. To achieve this, we predicted HLA class I and class II restricted peptides from rDEN2Δ30 and used them, in an IFN-gamma ELISPOT assay, to interrogate CD8(+) and CD4(+) T cell responses in healthy volunteers infected with rDEN2Δ30...
February 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28133798/tfh-cells-and-hiv-bnabs-an-immunodominance-model-of-the-hiv-neutralizing-antibody-generation-problem
#8
REVIEW
Colin Havenar-Daughton, Jeong Hyun Lee, Shane Crotty
The generation of HIV bnAbs may be one of the greatest feats of the human immune system and our best hope of finally creating an HIV vaccine. The striking amount of somatic hypermutation in HIV bnAbs led to the hypothesis that T follicular helper (Tfh) cells and germinal centers (GC) play a critical role in the ability of the immune system to generate these uncommon antibodies. In this review, we first summarize what is known about the immunological process of HIV bnAb development, the challenges of eliciting bnAbs via immunizations, and the putative central roles of Tfh cells and GC in the generation of HIV bnAbs...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28081174/definition-of-human-epitopes-recognized-in-tetanus-toxoid-and-development-of-an-assay-strategy-to-detect-ex-vivo-tetanus-cd4-t-cell-responses
#9
Ricardo da Silva Antunes, Sinu Paul, John Sidney, Daniela Weiskopf, Jennifer M Dan, Elizabeth Phillips, Simon Mallal, Shane Crotty, Alessandro Sette, Cecilia S Lindestam Arlehamn
Despite widespread uses of tetanus toxoid (TT) as a vaccine, model antigen and protein carrier, TT epitopes have been poorly characterized. Herein we defined the human CD4+ T cell epitope repertoire by reevaluation of previously described epitopes and evaluation of those derived from prediction of HLA Class II binding. Forty-seven epitopes were identified following in vitro TT stimulation, with 28 epitopes accounting for 90% of the total response. Despite this diverse range of epitopes, individual responses were associated with only a few immunodominant epitopes, with each donor responding on average to 3 epitopes...
2017: PloS One
https://www.readbyqxmd.com/read/28079888/antiphospholipid-antibodies-enhance-rat-neonatal-cardiomyocyte-apoptosis-in-an-in-vitro-hypoxia-reoxygenation-injury-model-via-p38-mapk
#10
Lauren T Bourke, Thomas McDonnell, James McCormick, Charis Pericleous, Vera M Ripoll, Ian Giles, Anisur Rahman, Anastasis Stephanou, Yiannis Ioannou
A significant amount of myocardial damage during a myocardial infarction (MI) occurs during the reperfusion stage, termed ischaemia/reperfusion (I/R) injury, and accounts for up to 50% of total infarcted tissue post-MI. During the reperfusion phase, a complex interplay of multiple pathways and mechanisms is activated, which ultimately leads to cell death, primarily through apoptosis. There is some evidence from a lupus mouse model that lupus IgG, specifically the antiphospholipid (aPL) antibody subset, is pathogenic in mesenteric I/R injury...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28079473/protective-immunity-against-influenza-in-hla-a2-transgenic-mice-by-modified-vaccinia-virus-ankara-vectored-vaccines-containing-internal-influenza-proteins
#11
Giuseppina Di Mario, Ester Sciaraffia, Marzia Facchini, Francesco Gubinelli, Elisa Soprana, Maddalena Panigada, Valentina Bernasconi, Bruno Garulli, Antonio Siccardi, Isabella Donatelli, Maria R Castrucci
BACKGROUND: The emergence of novel strains of influenza A viruses with hemagglutinins (HAs) that are antigenically distinct from those circulating in humans, and thus have pandemic potential, pose concerns and call for the development of more broadly protective influenza vaccines. In the present study, modified vaccinia virus Ankara (MVA) encoding internal influenza antigens were evaluated for their immunogenicity and ability to protect HLA-A2.1 transgenic (AAD) mice from infection with influenza viruses...
January 12, 2017: Pathogens and Global Health
https://www.readbyqxmd.com/read/28077659/hiv-controllers-exhibit-enhanced-frequencies-of-mhc-class-ii-tetramer-gag-specific-cd4-t-cells-in-chronic-clade-c-hiv-1-infection
#12
Faatima Laher, Srinika Ranasinghe, Filippos Porichis, Nikoshia Mewalal, Karyn Pretorius, Nasreen Ismail, Søren Buus, Anette Stryhn, Mary Carrington, Bruce D Walker, Thumbi Ndung'u, Zaza M Ndhlovu
: Immune control of viral infections is heavily dependent on helper CD4(+) T cell function. However, understanding the contribution of HIV-specific CD4(+) T cell responses to immune protection against HIV-1, particularly in clade C infection remains incomplete. Recently, MHC class II tetramers have emerged as a powerful tool for interrogating antigen specific CD4(+) T cells without relying on effector functions. Here, we defined the MHC class II alleles for immunodominant Gag CD4(+) T cell epitopes in clade C virus infection, constructed MHC class II tetramers, and then used these to define the magnitude, function, and relation to viral load of HIV-specific CD4(+) T cell responses in a cohort of untreated HIV clade C infected persons...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27998269/increased-t-cell-breadth-and-antibody-response-elicited-in-prime-boost-regimen-by-viral-vector-encoded-homologous-siv-gag-env-in-outbred-cd1-mice
#13
Anne-Marie Carola Andersson, Peter Johannes Holst
BACKGROUND: A major obstacle for the development of HIV vaccines is the virus' worldwide sequence diversity. Nevertheless, the presence of T cell epitopes within conserved regions of the virus' structural Gag protein and conserved structures in the envelope (env) sequence raises the possibility that cross-reactive responses may be induced by vaccination. In this study, the aim was to investigate the importance of antigenic match on immunodominance and breadth of obtainable T cell responses...
December 20, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27979027/immunodominance-in-allergic-t-cell-reactivity-to-japanese-cedar-in-different-geographic-cohorts
#14
Carla Oseroff, John Pham, April Frazier, Denise Hinz, John Sidney, Sinu Paul, Jason A Greenbaum, Randi Vita, Bjoern Peters, Véronique Schulten, Alessandro Sette
BACKGROUND: Japanese cedar (JC) pollen is a common trigger for allergic rhinitis in Japan. Pollen proteins targeted by IgE, including Cry j 1 and Cry j 2, and isoflavone reductase (IFR) have been identified. OBJECTIVE: To compare antigen-specific IgE titers and T-cell responses to JC pollen-derived extract and peptides in cohorts with high and low pollen exposure. METHODS: Peripheral blood mononuclear cells from JC pollen allergic or nonallergic patients who have lived in Japan for at least 1 year and JC pollen allergic patients who have never been to Japan were tested for T-cell responses against JC pollen extract and peptide pools derived from Cry j 1, Cry j 2, or IFR...
December 2016: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/27938705/antibody-profiling-of-canine-igg-responses-to-the-ospc-protein-of-the-lyme-disease-spirochetes-supports-a-multivalent-approach-in-vaccine-and-diagnostic-assay-development
#15
Lee D Oliver, Christopher G Earnhart, DeLacy Virginia-Rhodes, Michael Theisen, Richard T Marconi
OspC performs essential functions during the enzootic cycle of the Lyme disease (LD) spirochetes. In this study, the specificity of antibody (Ab) responses to OspC was profiled to define the antigenic determinants during infection and after vaccination. Several OspC variants or 'types' were screened with serum from SNAP4Dx C6 positive dogs and with serum from rabbits hyperimmunized with OspC proteins. The OspC type-specific nature of the Ab response revealed that variable domains of OspC are immunodominant during infection and upon vaccination...
December 2016: Veterinary Journal
https://www.readbyqxmd.com/read/27917626/association-of-new-putative-epitopes-of-myelin-proteolipid-protein-58-74-with-pathogenesis-of-multiple-sclerosis
#16
Zahra Zamanzadeh, Ghasem Ahangari, Mitra Ataei, Samie Pouragahi, Seyed Massood Nabavi, Mehdi Sadeghi, Mohammad Hossein Sanati
Multiple sclerosis (MS) is an autoimmune disease in which auto-reactive T cells react with self-antigens expressed in the central nervous system (CNS). The main cause of MS is unknown. Nonetheless, the most probable theory is based on molecular mimicry, which suggests that some infections can activate T cells against brain auto-antigens like myelin proteolipid protein (PLP) and initiate the disease cascade. This study is conducted to evaluate the activatory effects of PLP58-74 on T lymphocytes and humoral immunity...
October 2016: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/27914462/recombinant-mhc-tetramers-for-isolation-of-virus-specific-cd8-cells-from-healthy-donors-potential-approach-for-cell-therapy-of-posttransplant-cytomegalovirus-infection
#17
A S Vdovin, S Y Filkin, P R Yefimova, S A Sheetikov, N M Kapranov, Y O Davydova, E S Egorov, E G Khamaganova, M Y Drokov, L A Kuzmina, E N Parovichnikova, G A Efimov, V G Savchenko
Patients undergoing allogeneic hematopoietic stem cell transplantation have a high risk of cytomegalovirus reactivation, which in the absence of T-cell immunity can result in the development of an acute inflammatory reaction and damage of internal organs. Transfusion of the virus-specific donor T-lymphocytes represents an alternative to a highly toxic and often ineffective antiviral therapy. Potentially promising cell therapy approach comprises transfusion of cytotoxic T-lymphocytes, specific to the viral antigens, immediately after their isolation from the donor's blood circulation without any in vitro expansion...
November 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27902386/establishment-of-memory-cd8-t-cells-with-live-attenuated-influenza-virus-across-different-vaccination-doses
#18
Zhongfang Wang, Lukasz Kedzierski, Simone Nuessing, Brendon Yew Loong Chua, Sergio M Quiñones-Parra, Victor C Huber, David C Jackson, Paul G Thomas, Katherine Kedzierska
FluMist has been used in children and adults for more than 10 years. As pre-existing CD8+ T cell memory pools can provide heterologous immunity against distinct influenza viruses, it is important to understand influenza-specific CD8+ T cell responses elicited by different live attenuated influenza virus (LAIV) regimens. In this study, we immunized mice intranasally with two different doses of live-attenuated PR8 virus (PR8 ts, H1N1), low and high, and then assessed protective efficacy by challenging animals with heterosubtypic X31-H3N2 virus at 6 weeks post-vaccination...
December 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27902325/targeting-naturally-occurring-epitope-variants-of-hepatitis-c-virus-with-high-affinity-t-cell-receptors
#19
Huajun Zhang, Jianbing Zhang, Lei Chen, Zhiming Weng, Ye Tian, Haifeng Zhao, Youjia Li, Lin Chen, Zhaoduan Liang, Hongjun Zheng, Wenzhuo Zhao, Shi Zhong, Yi Li
Hepatitis C virus (HCV) readily establishes chronic infection, which is characterized by failure of virus-specific CD8+ T cells. HCV uses epitope mutation and T-cell exhaustion to escape from the host immune response. Previously, we engineered high-affinity T-cell receptors (HATs) targeting HIV escape mutants. In this study, the affinity of a T-cell receptor specific for the human leukocyte antigen (HLA)-A2-restricted HCV immunodominant epitope NS3 1406-1415 (KLVALGINAV) was improved from a KD of 6.6 µM to 40 pM...
November 11, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27895172/pulmonary-dendritic-cell-subsets-shape-the-respiratory-syncytial-virus-specific-cd8-t-cell-immunodominance-hierarchy-in-neonates
#20
Allison M W Malloy, Tracy J Ruckwardt, Kaitlyn M Morabito, Annie W Lau-Kilby, Barney S Graham
Young infants are generally more susceptible to viral infections and experience more severe disease than do adults. CD8(+) T cells are important for viral clearance, and although often ineffective in neonates they can be protective when adequately stimulated. Using a murine CB6F1/J hybrid model of respiratory syncytial virus (RSV) infection, we previously demonstrated that the CD8(+) T cell immunodominance hierarchy to two RSV-derived epitopes, K(d)M282-90 and D(b)M187-195, was determined by the age at infection...
January 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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