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Immunodominant T cell

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https://www.readbyqxmd.com/read/29032899/th1-epitope-peptides-induce-protective-immunity-against-rickettsia-rickettsii-infection-in-c3h-hen-mice
#1
Wenping Gong, Xiaolu Xiong, Pengcheng Wang, Jun Jiao, Xiaomei Yang, Bohai Wen
Rickettsia rickettsii is the causative pathogen of Rocky Mountain spotted fever (RMSF). Adr2, YbgF and OmpB are protective antigens of R. rickettsii. In this study, 90 candidate peptides were selected from these antigens based on their high-affinity binding capacity for the MHC class II molecule H2 I-A or H2 I-E using bioinformatic methods. Six peptides were determined using ELISPOT assay to be immunodominant based on the IFN-γ recall responses of CD4(+) T cells from mice immunized with R. rickettsii. Six nucleotide sequences encoding the immunodominant peptides were linked in series and inserted into a plasmid for expression in Escherichia coli cells, resulting in a new, recombinant polypeptide termed GWP...
October 9, 2017: Vaccine
https://www.readbyqxmd.com/read/28993513/dna-vaccination-by-electroporation-amplifies-broadly-cross-restricted-public-tcr-clonotypes-shared-with-hiv-controllers
#2
Madhura Mukhopadhyay, Moran Galperin, Mandar Patgaonkar, Sandhya Vasan, David D Ho, Alexandre Nouël, Mathieu Claireaux, Daniela Benati, Olivier Lambotte, Yaoxing Huang, Lisa A Chakrabarti
Rare patients who spontaneously control HIV replication provide a useful model to inform HIV vaccine development. HIV controllers develop particularly efficient antiviral CD4(+) T cell responses mediated by shared high-affinity TCRs. To determine whether the candidate DNA vaccine ADVAX could induce similar responses, we analyzed Gag-specific primary CD4(+) T cells from healthy volunteers who received ADVAX DNA by electroporation. Vaccinated volunteers had an immunodominant response to the Gag293 epitope with a functional avidity intermediate between that of controllers and treated patients...
October 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28975614/t-cell-receptor-alpha-variable-12-2-bias-in-the-immunodominant-response-to-yellow-fever-virus
#3
Amandine Bovay, Vincent Zoete, Garry Dolton, Anna M Bulek, David K Cole, Pierre J Rizkallah, Anna Fuller, Konrad Beck, Olivier Michielin, Daniel E Speiser, Andrew K Sewell, Silvia A Fuertes Marraco
The repertoire of human αβ T cell receptors (TCRs) is generated via somatic recombination of germline gene segments. Despite this enormous variation, certain epitopes can be immunodominant, associated with high frequencies of antigen-specific T cells and/or exhibit bias towards a TCR gene segment. Here, we studied the TCR repertoire of the HLA-A*0201-restricted epitope LLWNGPMAV (hereafter, A2/LLW) from Yellow Fever virus, which generates an immunodominant CD8(+) T cell response to the highly effective YF-17D vaccine...
October 3, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28968792/control-of-hiv-1-by-an-hla-b-52-01-c-12-02-protective-haplotype
#4
Takayuki Chikata, Hayato Murakoshi, Madoka Koyanagi, Kazutaka Honda, Hiroyuki Gatanaga, Shinichi Oka, Masafumi Takiguchi
HLA-B*52:01-C*12:02, which is found in approximately 20 % of all Japanese, is well known to be associated with ulcerative colitis and Takayasu arteritis. This haplotype is also known to be a protective one in HIV-1-infective individuals. Recent studies showed that HLA-B*52:01-restricted HIV-1-specific T cells suppress HIV-1 and that HLA-C*12:02 together with KIR2DL2 play an important role in NK cell-mediated control of HIV-1. However, the role of HLA-C*12:02-restricted CTLs in suppression of HIV-1 replication remains unknown...
September 14, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28959348/in-silico-perspectives-on-the-prediction-of-the-plp-s-epitopes-involved-in-multiple-sclerosis
#5
Zahra Zamanzadeh, Mitra Ataei, Seyed Massood Nabavi, Ghasem Ahangari, Mehdi Sadeghi, Mohammad Hosein Sanati
BACKGROUND: Multiple sclerosis (MS) is the most common autoimmune disease of the central nervous system (CNS). The main cause of the MS is yet to be revealed, but the most probable theory is based on the molecular mimicry that concludes some infections in the activation of T cells against brain auto-antigens that initiate the disease cascade. OBJECTIVES: The Purpose of this research is the prediction of the auto-antigen potency of the myelin proteolipid protein (PLP) in multiple sclerosis...
March 2017: Iranian journal of biotechnology
https://www.readbyqxmd.com/read/28959261/a-novel-approach-to-reinstating-tolerance-in-experimental-autoimmune-myasthenia-gravis-using-a-targeted-fusion-protein-mcta1-t146
#6
Alessandra Consonni, Sapna Sharma, Karin Schön, Cristina Lebrero-Fernández, Elena Rinaldi, Nils Yngve Lycke, Fulvio Baggi
Reinstating tissue-specific tolerance has attracted much attention as a means to treat autoimmune diseases. However, despite promising results in rodent models of autoimmune diseases, no established tolerogenic therapy is clinically available yet. In the experimental autoimmune myasthenia gravis (EAMG) model several protocols have been reported that induce tolerance against the prime disease-associated antigen, the acetylcholine receptor (AChR) at the neuromuscular junction. Using the whole AChR, the extracellular part or peptides derived from the receptor, investigators have reported variable success with their treatments, though, usually relatively large amounts of antigen has been required...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28957443/a-glycosylated-recombinant-subunit-candidate-vaccine-consisting-of-ehrlichia-ruminantium-major-antigenic-protein1-induces-specific-humoral-and-th1-type-cell-responses-in-sheep
#7
Bonto Faburay, Jodi McGill, Frans Jongejan
Heartwater, or cowdriosis, is a tick-borne disease of domestic and wild ruminants that is endemic in the Caribbean and sub-Saharan Africa. The disease is caused by an intracellular pathogen, Ehrlichia ruminantium and may be fatal within days of the onset of clinical signs with mortality rates of up to 90% in susceptible hosts. Due to the presence of competent tick vectors in North America, there is substantial risk of introduction of heartwater with potentially devastating consequences to the domestic livestock industry...
2017: PloS One
https://www.readbyqxmd.com/read/28950731/unbiased-identification-of-t-cell-receptors-targeting-immunodominant-peptide-mhc-complexes-for-t-cell-receptor-immunotherapy
#8
Felix K M Lorenz, Christian Ellinger, Elisa Kieback, Susanne Wilde, Maria Lietz, Dolores J Schendel, Wolfgang Uckert
T cell receptor (TCR) immunotherapy uses T cells engineered with new TCRs to enable detection and killing of cancer cells. Efficacy of TCR immunotherapy depends on targeting antigenic peptides that are efficiently presented by the best suited major histocompatibility complex (MHC) molecules of cancer cells. However, efficient strategies are lacking to easily identify TCRs recognizing immunodominant peptide-MHC (pMHC) combinations utilizing any of the six possible MHC class I alleles of a cancer cell. We generated an MHC cell library and developed a platform approach to detect, isolate and re-express TCRs specific for immunodominant pMHCs...
September 26, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28945243/germline-bias-dictates-cross-serotype-reactivity-in-a-common-dengue-virus-specific-cd8-t-cell-response
#9
Abigail Culshaw, Kristin Ladell, Stephanie Gras, James E McLaren, Kelly L Miners, Carine Farenc, Heleen van den Heuvel, Emma Gostick, Wanwisa Dejnirattisai, Apirath Wangteeraprasert, Thaneeya Duangchinda, Pojchong Chotiyarnwong, Wannee Limpitikul, Sirijitt Vasanawathana, Prida Malasit, Tao Dong, Jamie Rossjohn, Juthathip Mongkolsapaya, David A Price, Gavin R Screaton
Adaptive immune responses protect against infection with dengue virus (DENV), yet cross-reactivity with distinct serotypes can precipitate life-threatening clinical disease. We found that clonotypes expressing the T cell antigen receptor (TCR) β-chain variable region 11 (TRBV11-2) were 'preferentially' activated and mobilized within immunodominant human-leukocyte-antigen-(HLA)-A*11:01-restricted CD8(+) T cell populations specific for variants of the nonstructural protein epitope NS3133 that characterize the serotypes DENV1, DENV3 and DENV4...
September 25, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28940167/th2-biased-immune-response-and-agglutinating-antibodies-generation-by-a-chimeric-protein-comprising-ompc-epitope-323-336-of-aeromonas-hydrophila-and-ltb
#10
Mahima Sharma, Pujarini Dash, Pramod K Sahoo, Aparna Dixit
Aeromonas hydrophila is responsible for causing fatal infections in freshwater fishes. Besides chemical/antibiotic treatment and whole-cell vaccine, no subunit vaccine is currently available for A. hydrophila. Outer membrane proteins of gram-negative bacteria have been reported as effective vaccine candidates. Peptide antigens elicit focused immune responses against immunodominant stretches of the antigen. We have attempted to characterize the immunogenicity of linear B-cell epitopes of outer membrane protein (OmpC) of A...
September 22, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28939855/infection-with-burkholderia-pseudomallei-immune-correlates-of-survival-in-acute-melioidosis
#11
Susanna J Dunachie, Kemajittra Jenjaroen, Catherine J Reynolds, Kathryn J Quigley, Ruhena Sergeant, Manutsanun Sumonwiriya, Panjaporn Chaichana, Suchintana Chumseng, Pitchayanant Ariyaprasert, Patricia Lassaux, Louise Gourlay, Charuporn Promwong, Prapit Teparrukkul, Direk Limmathurotsakul, Nicholas P J Day, Daniel M Altmann, Rosemary J Boyton
Melioidosis, caused by Burkholderia pseudomallei, is a potentially lethal infection with no licensed vaccine. There is little understanding of why some exposed individuals have no symptoms, while others rapidly progress to sepsis and death, or why diabetes confers increased susceptibility. We prospectively recruited a cohort of 183 acute melioidosis patients and 21 control subjects from Northeast Thailand and studied immune parameters in the context of survival status and the presence or absence of diabetes...
September 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28939757/pd-1-blockade-promotes-epitope-spreading-in-anticancer-cd8-t-cell-responses-by-preventing-fratricidal-death-of-subdominant-clones-to-relieve-immunodomination
#12
Arash Memarnejadian, Courtney E Meilleur, Christopher R Shaler, Khashayarsha Khazaie, Jack R Bennink, Todd D Schell, S M Mansour Haeryfar
The interactions between programmed death-1 (PD-1) and its ligands hamper tumor-specific CD8(+) T cell (TCD8) responses, and PD-1-based "checkpoint inhibitors" have shown promise in certain cancers, thus revitalizing interest in immunotherapy. PD-1-targeted therapies reverse TCD8 exhaustion/anergy. However, whether they alter the epitope breadth of TCD8 responses remains unclear. This is an important question because subdominant TCD8 are more likely than immunodominant clones to escape tolerance mechanisms and may contribute to protective anticancer immunity...
September 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28938005/recombinant-vaccines-of-a-cd4-t-cell-epitope-promote-efficient-control-of-paracoccidioides-brasiliensis-burden-by-restraining-primary-organ-infection
#13
Rodrigo Assunção Holanda, Julián Esteban Muñoz, Lucas Santos Dias, Leandro Buffoni Roque Silva, Julliana Ribeiro Alves Santos, Sthefany Pagliari, Érica Leandro Marciano Vieira, Tatiane Alves Paixão, Carlos Pelleschi Taborda, Daniel Assis Santos, Oscar Bruña-Romero
Paracoccidioidomycosis (PCM) is an infectious disease endemic to South America, caused by the thermally dimorphic fungi Paracoccidioides. Currently, there is no effective human vaccine that can be used in prophylactic or therapeutic regimes. We tested the hypothesis that the immunogenicity of the immunodominant CD4+ T-cell epitope (P10) of Paracoccidioides brasiliensis gp43 antigen might be significantly enhanced by using a hepatitis B virus-derived particle (VLP) as an antigen carrier. This chimera was administered to mice as a (His)6-purified protein (rPbT) or a replication-deficient human type 5 adenoviral vector (rAdPbT) in an immunoprophylaxis assay...
September 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28935714/profiling-mhc-ii-immunopeptidome-of-blood-stage-malaria-reveals-that-cdc1-control-the-functionality-of-parasite-specific-cd4-t-cells
#14
Marion Draheim, Myriam F Wlodarczyk, Karine Crozat, Jean-Michel Saliou, Tchilabalo Dilezitoko Alayi, Stanislas Tomavo, Ali Hassan, Anna Salvioni, Claudia Demarta-Gatsi, John Sidney, Alessandro Sette, Marc Dalod, Antoine Berry, Olivier Silvie, Nicolas Blanchard
In malaria, CD4 Th1 and T follicular helper (TFH) cells are important for controlling parasite growth, but Th1 cells also contribute to immunopathology. Moreover, various regulatory CD4 T-cell subsets are critical to hamper pathology. Yet the antigen-presenting cells controlling Th functionality, as well as the antigens recognized by CD4 T cells, are largely unknown. Here, we characterize the MHC II immunopeptidome presented by DC during blood-stage malaria in mice. We establish the immunodominance hierarchy of 14 MHC II ligands derived from conserved parasite proteins...
September 21, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28934427/immunologic-profiling-of-human-metapneumovirus-for-the-development-of-targeted-immunotherapy
#15
Ifigeneia Tzannou, Sarah K Nicholas, Premal Lulla, Paibel I Aguayo-Hiraldo, Anisha Misra, Caridad A Martinez, Annette A Machado, Jordan S Orange, Pedro A Piedra, Juan F Vera, Ann M Leen
Human metapneumovirus (hMPV) is a respiratory virus detected in ≥9% of allogeneic hematopoietic stem cell transplant (HSCT) recipients, in whom it can cause significant morbidity and mortality. Given the lack of effective antivirals, we investigated the potential for immunotherapeutic intervention, using adoptively transferred T cells. Thus, we characterized the cellular immune response to the virus and identified F, N, M2-1, M, and P as immunodominant target antigens. Reactive T cells were polyclonal (ie, they expressed CD4 and CD8), T-helper type 1 polarized, and polyfunctional (ie, they produced interferon γ, tumor necrosis factor α, granulocyte-macrophage colony-stimulating factor, and granzyme B), and they were able to kill autologous antigen-loaded targets...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28931830/circulating-mycobacterium-tuberculosis-dosr-latency-antigen-specific-polyfunctional-regulatory-il10-th17-cd4-t-cells-differentiate-latent-from-active-tuberculosis
#16
Srabanti Rakshit, Vasista Adiga, Soumya Nayak, Pravat Nalini Sahoo, Prabhat Kumar Sharma, Krista E van Meijgaarden, Anto Jesuraj Uk J, Chirag Dhar, George D Souza, Greg Finak, Stephen C De Rosa, Tom H M Ottenhoff, Annapurna Vyakarnam
The functional heterogeneity of T cell responses to diverse antigens expressed at different stages of Mycobacterium tuberculosis (Mtb) infection, in particular early secreted versus dormancy related latency antigens expressed later, that distinguish subjects with latent (LTBI), pulmonary (PTB) or extrapulmonary (EPTB) tuberculosis remains unclear. Here we show blood central memory CD4 T-cell responses specific to Mtb dormancy related (DosR) latency, but not classical immunodominant secretory antigens, to clearly differentiate LTBI from EPTB and PTB...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931605/structural-basis-for-clonal-diversity-of-the-human-t-cell-response-to-a-dominant-influenza-virus-epitope
#17
Xinbo Yang, Guobing Chen, Nan-Ping Weng, Roy A Mariuzza
Influenza A virus (IAV) causes an acute infection in humans that is normally eliminated by CD8+ cytotoxic T lymphocytes. Individuals expressing the major histocompatibility complex (MHC) class I molecule HLA-A2 produce cytotoxic T lymphocytes bearing T cell receptors (TCRs) that recognize the immunodominant IAV epitope GILGFVFTL (GIL). Most GIL-specific TCRs utilize α/β pairs encoded by the TRAV27/TRBV19 gene combination to recognize this relatively featureless peptide epitope (canonical TCRs). However, ~40% of GIL-specific TCRs express a wide variety of other TRAV/TRBV combinations (non-canonical TCRs)...
September 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28893919/antigen-localisation-influences-the-magnitude-and-kinetics-of-the-endogenous-adaptive-immune-response-to-recombinant-salmonella-vaccines
#18
Yanina R Sevastsyanovich, David R Withers, Claire L Marriott, Faye C Morris, Timothy J Wells, Douglas F Browning, Irene Beriotto, Ewan Ross, Hossam Omar Ali, Catherine A Wardius, Adam F Cunningham, Ian R Henderson, Amanda E Rossiter
The use of recombinant attenuated Salmonella vaccine (RASV) strains is a promising strategy to present heterologous antigens to the mammalian immune system to induce both cellular and humoral immune responses. However, studies on RASV development differ in where heterologous antigens are expressed and localised within the bacterium and it is unclear how antigen localisation modulates the immune response. Previously, we exploited the plasmid-encoded toxin (Pet) autotransporter system for accumulation of heterologous antigens in the cell culture supernatant...
September 11, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28887632/multipeptide-coupled-nanoparticles-induce-tolerance-in-humanised-hla-transgenic-mice-and-inhibit-diabetogenic-cd8-t-cell-responses-in-type-1-diabetes
#19
Xinyu Xu, Lingling Bian, Min Shen, Xin Li, Jing Zhu, Shuang Chen, Lei Xiao, Qingqing Zhang, Heng Chen, Kuanfeng Xu, Tao Yang
AIMS/HYPOTHESIS: Induction of antigen-specific immunological tolerance may provide an attractive immunotherapy in the NOD mouse model but the conditions that lead to the successful translation to human type 1 diabetes are limited. In this study, we covalently linked 500 nm carboxylated polystyrene beads (PSB) with a mixture of immunodominant HLA-A*02:01-restricted epitopes (peptides-PSB) that may have high clinical relevance in humans as they promote immune tolerance; we then investigated the effect of the nanoparticle-peptide complexes on T cell tolerance...
September 8, 2017: Diabetologia
https://www.readbyqxmd.com/read/28878138/stereotyped-antibody-responses-target-posttranslationally-modified-gluten-in-celiac-disease
#20
Omri Snir, Xi Chen, Moriah Gidoni, M Fleur du Pré, Yuguang Zhao, Øyvind Steinsbø, Knut Ea Lundin, Gur Yaari, Ludvig M Sollid
The role of B cells and posttranslational modifications in pathogenesis of organ-specific immune diseases is increasingly envisioned but remains poorly understood, particularly in human disorders. In celiac disease, transglutaminase 2-modified (TG2-modified; deamidated) gluten peptides drive disease-specific T cell and B cell responses, and antibodies to deamidated gluten peptides are excellent diagnostic markers. Here, we substantiate by high-throughput sequencing of IGHV genes that antibodies to a disease-specific, deamidated, and immunodominant B cell epitope of gluten (PLQPEQPFP) have biased and stereotyped usage of IGHV3-23 and IGHV3-15 gene segments with modest somatic mutations...
September 7, 2017: JCI Insight
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