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Immunodominant T cell

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https://www.readbyqxmd.com/read/28326672/bk-polyomavirus-specific-9mer-cd8-t-cell-responses-correlate-with-clearance-of-bk-viremia-in-kidney-transplant-recipients-first-report-from-the-swiss-transplant-cohort-study-stcs
#1
Céline Leboeuf, Sabrina Wilk, Rita Achermann, Isabelle Binet, Dela Golshayan, Karin Hadaya, Cedric Hirzel, Matthias Hoffmann, Uyen Huynh-Do, Michael T Koller, Oriol Manuel, Nicolas J Mueller, Thomas F Mueller, Stefan Schaub, Christian van Delden, Fabian H Weissbach, Hans H Hirsch
BK polyomavirus (BKPyV) causes premature kidney transplant (KT) failure in 1-15% of patients. Since antivirals are lacking, most programs screen for BKPyV-viremia and, if positive, reduce immunosuppression. To evaluate the relationship of viremia and BKPyV-specific immunity, we examined prospectively cryopreserved plasma and PBMCs at T0, T6, and T12 months post-transplant from 28 viremic KT patients and 68 non-viremic controls matched for the transplantation period. BKPyV-IgG seroprevalence was comparable between cases (89...
March 22, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28315221/t-cell-proliferation-assay-determination-of-immunodominant-t-cell-epitopes-of-food-allergens
#2
Madhan Masilamani, Mariona Pascal, Hugh A Sampson
Characterization of allergen-specific T cells is critical to understand their contribution to disease pathogenesis. The identification of immunodominant T-cell epitopes is crucial for development of T-cell-based vaccines. Peptide-specific T-cell proliferation studies are usually performed in a library of short synthetic peptides (15mer or 20mer) with 3 or 5 offset spanning the entire length of the allergen. T-cell peptide epitopes lack the primary and tertiary structure of the native protein to cross-link IgE, but retain the ability to stimulate T cells...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28288094/identification-of-zika-virus-epitopes-reveals-immunodominant-and-protective-roles-for-dengue-virus-cross-reactive-cd8-t-cells
#3
Jinsheng Wen, William Weihao Tang, Nicholas Sheets, Julia Ellison, Alessandro Sette, Kenneth Kim, Sujan Shresta
CD8(+) T cells play an important role in controlling Flavivirus infection, including Zika virus (ZIKV). Here, we have identified 25 HLA-B*0702-restricted epitopes and 1 HLA-A*0101-restricted epitope using interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) and intracellular cytokine staining (ICS) in ZIKV-infected IFN-α/β receptor-deficient HLA transgenic mice. The cross-reactivity of ZIKV epitopes to dengue virus (DENV) was tested using IFN-γ-ELISPOT and IFN-γ-ICS on CD8(+) T cells from DENV-infected mice, and five cross-reactive HLA-B*0702-binding peptides were identified by both assays...
March 13, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28275375/a-comparative-phase-i-study-of-combination-homologous-subtype-c-dna-mva-and-env-gp140-protein-adjuvant-hiv-vaccines-in-two-immunization-regimes
#4
Sarah Joseph, Killian Quinn, Aldona Greenwood, Alethea V Cope, Paul F McKay, Peter J Hayes, Jakub T Kopycinski, Jill Gilmour, Aleisha N Miller, Christof Geldmacher, Yuka Nadai, Mohamed I M Ahmed, David C Montefiori, Len Dally, George Bouliotis, David J M Lewis, Roger Tatoud, Ralf Wagner, Mariano Esteban, Robin J Shattock, Sheena McCormack, Jonathan Weber
There remains an urgent need for a prophylactic HIV vaccine. We compared combined MVA and adjuvanted gp140 to sequential MVA/gp140 after DNA priming. We expected Env-specific CD4+ T-cells after DNA and MVA priming, and Env-binding antibodies in 100% individuals after boosting with gp140 and that combined vaccines would not compromise safety and might augment immunogenicity. Forty volunteers were primed three times with DNA plasmids encoding (CN54) env and (ZM96) gag-pol-nef at 0, 4 and 8 weeks then boosted with MVA-C (CN54 env and gag-pol-nef) and glucopyranosyl lipid adjuvant-aqueous formulation (GLA-AF) adjuvanted CN54gp140...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28270111/an-optimized-ifn-%C3%AE-elispot-assay-for-the-sensitive-and-standardized-monitoring-of-cmv-protein-reactive-effector-cells-of-cell-mediated-immunity
#5
Sascha Barabas, Theresa Spindler, Richard Kiener, Charlotte Tonar, Tamara Lugner, Julia Batzilla, Hanna Bendfeldt, Anne Rascle, Benedikt Asbach, Ralf Wagner, Ludwig Deml
BACKGROUND: In healthy individuals, Cytomegalovirus (CMV) infection is efficiently controlled by CMV-specific cell-mediated immunity (CMI). Functional impairment of CMI in immunocompromized individuals however can lead to uncontrolled CMV replication and severe clinical complications. Close monitoring of CMV-specific CMI is therefore clinically relevant and might allow a reliable prognosis of CMV disease as well as assist personalized therapeutic decisions. METHODS: Objective of this work was the optimization and technical validation of an IFN-γ ELISpot assay for a standardized, sensitive and reliable quantification of CMV-reactive effector cells...
March 7, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28250417/broad-tcr-repertoire-and-diverse-structural-solutions-for-recognition-of-an-immunodominant-cd8-t-cell-epitope
#6
InYoung Song, Anna Gil, Rabinarayan Mishra, Dario Ghersi, Liisa K Selin, Lawrence J Stern
A keystone of antiviral immunity is CD8(+) T cell recognition of viral peptides bound to MHC-I proteins. The recognition modes of individual T cell receptors (TCRs) have been studied in some detail, but the role of TCR variation in providing a robust response to viral antigens is unclear. The influenza M1 epitope is an immunodominant target of CD8(+) T cells that help to control influenza in HLA-A2(+) individuals. Here we show that CD8(+) T cells use many distinct TCRs to recognize HLA-A2-M1, which enables the use of different structural solutions to the problem of specifically recognizing a relatively featureless peptide antigen...
February 27, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28228754/proofreading-of-peptide-mhc-complexes-through-dynamic-multivalent-interactions
#7
REVIEW
Christoph Thomas, Robert Tampé
The adaptive immune system is able to detect and destroy cells that are malignantly transformed or infected by intracellular pathogens. Specific immune responses against these cells are elicited by antigenic peptides that are presented on major histocompatibility complex class I (MHC I) molecules and recognized by cytotoxic T lymphocytes at the cell surface. Since these MHC I-presented peptides are generated in the cytosol by proteasomal protein degradation, they can be metaphorically described as a window providing immune cells with insights into the state of the cellular proteome...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28218747/mhc-i-peptides-get-out-of-the-groove-and-enable-a-novel-mechanism-of-hiv-1-escape
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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...
March 2017: Pathogens and Global Health
https://www.readbyqxmd.com/read/28077659/hiv-controllers-exhibit-enhanced-frequencies-of-major-histocompatibility-complex-class-ii-tetramer-gag-specific-cd4-t-cells-in-chronic-clade-c-hiv-1-infection
#19
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, the understanding of the contribution of HIV-specific CD4(+) T cell responses to immune protection against HIV-1, particularly in clade C infection, remains incomplete. Recently, major histocompatibility complex (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 the viral load of HIV-specific CD4(+) T cell responses in a cohort of untreated HIV clade C-infected persons...
April 1, 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
#20
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
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