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T cell epitope

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https://www.readbyqxmd.com/read/29166592/hiv-envelope-glycoform-heterogeneity-and-localized-diversity-govern-the-initiation-and-maturation-of-a-v2-apex-broadly-neutralizing-antibody-lineage
#1
Elise Landais, Ben Murrell, Bryan Briney, Sasha Murrell, Kimmo Rantalainen, Zachary T Berndsen, Alejandra Ramos, Lalinda Wickramasinghe, Melissa Laird Smith, Kemal Eren, Natalia de Val, Mengyu Wu, Audrey Cappelletti, Jeffrey Umotoy, Yolanda Lie, Terri Wrin, Paul Algate, Po-Ying Chan-Hui, Etienne Karita, Andrew B Ward, Ian A Wilson, Dennis R Burton, Davey Smith, Sergei L Kosakovsky Pond, Pascal Poignard
Understanding how broadly neutralizing antibodies (bnAbs) to HIV envelope (Env) develop during natural infection can help guide the rational design of an HIV vaccine. Here, we described a bnAb lineage targeting the Env V2 apex and the Ab-Env co-evolution that led to development of neutralization breadth. The lineage Abs bore an anionic heavy chain complementarity-determining region 3 (CDRH3) of 25 amino acids, among the shortest known for this class of Abs, and achieved breadth with only 10% nucleotide somatic hypermutation and no insertions or deletions...
November 21, 2017: Immunity
https://www.readbyqxmd.com/read/29164053/synergistic-protective-activity-of-tumor-specific-epitopes-engineered-in-bacterial-outer-membrane-vesicles
#2
Alberto Grandi, Michele Tomasi, Ilaria Zanella, Luisa Ganfini, Elena Caproni, Laura Fantappiè, Carmela Irene, Luca Frattini, Samine J Isaac, Enrico König, Francesca Zerbini, Simona Tavarini, Chiara Sammicheli, Fabiola Giusti, Ilaria Ferlenghi, Matteo Parri, Guido Grandi
Introduction: Bacterial outer membrane vesicles (OMVs) are naturally produced by all Gram-negative bacteria and, thanks to their plasticity and unique adjuvanticity, are emerging as an attractive vaccine platform. To test the applicability of OMVs in cancer immunotherapy, we decorated them with either one or two protective epitopes present in the B16F10EGFRvIII cell line and tested the protective activity of OMV immunization in C57BL/6 mice challenged with B16F10EGFRvIII. Materials and methods: The 14 amino acid B cell epitope of human epidermal growth factor receptor variant III (EGFRvIII) and the mutation-derived CD4+ T cell neo-epitope of kif18b gene (B16-M30) were used to decorate OMVs either alone or in combination...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29163514/an-unexpected-major-role-for-proteasome-catalyzed-peptide-splicing-in-generation-of-t-cell-epitopes-is-there-relevance-for-vaccine-development
#3
REVIEW
Anouk C M Platteel, Juliane Liepe, Willem van Eden, Michele Mishto, Alice J A M Sijts
Efficient and safe induction of CD8(+) T cell responses is a desired characteristic of vaccines against intracellular pathogens. To achieve this, a new generation of safe vaccines is being developed accommodating single, dominant antigens of pathogens of interest. In particular, the selection of such antigens is challenging, since due to HLA polymorphism the ligand specificities and immunodominance hierarchies of pathogen-specific CD8(+) T cell responses differ throughout the human population. A recently discovered mechanism of proteasome-mediated CD8(+) T cell epitope generation, i...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163442/the-rationale-for-a-preventative-hcv-virus-like-particle-vlp-vaccine
#4
REVIEW
Joseph Torresi
HCV represents a global health problem with ~200 million individuals currently infected, worldwide. With the high cost of antiviral therapies, the global burden of chronic hepatitis C infection (CHCV) infection will be substantially reduced by the development of an effective vaccine for HCV. The field of HCV vaccines is generally divided into proponents of strategies to induce neutralizing antibodies (NAb) and those who propose to elicit cell mediated immunity (CMI). However, for a hepatitis C virus (HCV) vaccine to be effective in preventing infection, it must be capable of generating cross-reactive CD4+, CD8+ T cell, and NAb responses that will cover the major viral genotypes...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29157448/ab-initio-conformational-epitope-structure-prediction-using-genetic-algorithm-and-svm-for-vaccine-design
#5
Basem Ameen Moghram, Emad Nabil, Amr Badr
BACKGROUND AND OBJECTIVE: T-cell epitope structure identification is a significant challenging immunoinformatic problem within epitope-based vaccine design. Epitopes or antigenic peptides are a set of amino acids that bind with the Major Histocompatibility Complex (MHC) molecules. The aim of this process is presented by Antigen Presenting Cells to be inspected by T-cells. MHC-molecule-binding epitopes are responsible for triggering the immune response to antigens. The epitope's three-dimensional (3D) molecular structure (i...
January 2018: Computer Methods and Programs in Biomedicine
https://www.readbyqxmd.com/read/29157291/vaccination-with-recombinant-adenovirus-expressing-peste-des-petits-ruminants-virus-f-or-h-proteins-elicits-t-cell-responses-to-epitopes-that-arises-during-pprv-infection
#6
José Manuel Rojas, Miguel Avia, Elena Pascual, Noemí Sevilla, Verónica Martín
Peste des petits ruminants virus (PPRV) causes an economically important disease that limits productivity in small domestic ruminants and often affects the livestock of the poorest populations in developing countries. Animals that survive PPRV develop strong cellular and humoral responses, which are probably necessary for protection. Vaccination should thus aim at mimicking these natural responses. Immunization strategies against this morbillivirus using recombinant adenoviruses expressing PPRV-F or -H proteins can protect PPRV-challenged animals and permit differentiation of infected from vaccinated animals...
November 21, 2017: Veterinary Research
https://www.readbyqxmd.com/read/29155844/hypoxia-and-hypoxia-inducible-factor-hif-downregulate-antigen-presenting-mhc-class-i-molecules-limiting-tumor-cell-recognition-by-t-cells
#7
Shalini Sethumadhavan, Murillo Silva, Phaethon Philbrook, Thao Nguyen, Stephen M Hatfield, Akio Ohta, Michail V Sitkovsky
Human cancers are known to downregulate Major Histocompatibility Complex (MHC) class I expression thereby escaping recognition and rejection by anti-tumor T cells. Here we report that oxygen tension in the tumor microenvironment (TME) serves as an extrinsic cue that regulates antigen presentation by MHC class I molecules. In support of this view, hypoxia is shown to negatively regulate MHC expression in a HIF-dependent manner as evidenced by (i) lower MHC expression in the hypoxic TME in vivo and in hypoxic 3-dimensional (3D) but not 2-dimensional (2D) tumor cell cultures in vitro; (ii) decreased MHC in human renal cell carcinomas with constitutive expression of HIF due to genetic loss of von Hippel-Lindau (VHL) function as compared with isogenically paired cells with restored VHL function, and iii) increased MHC in tumor cells with siRNA-mediated knockdown of HIF...
2017: PloS One
https://www.readbyqxmd.com/read/29151181/screening-hcv-genotype-specific-epitope-peptides-based-on-conserved-sequence-analysis-and-b-cell-epitope-prediction-in-hcv-e2-region
#8
Rui Hua, Xiaoyu Jiang, Lingxia Qi, Shanshan Guan, Ziyu Kuai, Yongbo Qiao, Yan Xu, Xin Gong, Yuhua Shi, Wei Kong, Junqi Niu, Hao Zhang, Yaming Shan
The high mutation rate of the hepatitis C virus (HCV) genome increases the genotype diversity and renders the detection of the virus more difficult. Therefore, prediction and assessment of highly conserved and strongly antigenic epitope polypeptide sequences have become a focus of current research. The E2 region is the target binding region of neutralizing antibodies. HCV genomics, especially the high mutation rate of E2 region sequence, makes its genotyping more and more diverse, and the detection of HCV and genotype is becoming more and more strict...
November 18, 2017: Immunologic Research
https://www.readbyqxmd.com/read/29150238/a-t-cell-receptor-locus-harbors-a-malaria-specific-immune-response-gene
#9
Natalija Van Braeckel-Budimir, Stephanie Gras, Kristin Ladell, Tracy M Josephs, Lecia Pewe, Stina L Urban, Kelly L Miners, Carine Farenc, David A Price, Jamie Rossjohn, John T Harty
Immune response (Ir) genes, originally proposed by Baruj Benacerraf to explain differential antigen-specific responses in animal models, have become synonymous with the major histocompatibility complex (MHC). We discovered a non-MHC-linked Ir gene in a T cell receptor (TCR) locus that was required for CD8(+) T cell responses to the Plasmodium berghei GAP5040-48 epitope in mice expressing the MHC class I allele H-2D(b). GAP5040-48-specific CD8(+) T cell responses emerged from a very large pool of naive Vβ8...
November 21, 2017: Immunity
https://www.readbyqxmd.com/read/29147614/exploiting-a-new-strategy-to-induce-immunogenic-cell-death-to-improve-dendritic-cell-based-vaccines-for-lymphoma-immunotherapy
#10
B Montico, C Lapenta, M Ravo, D Martorelli, E Muraro, B Zeng, E Comaro, M Spada, S Donati, S M Santini, R Tarallo, G Giurato, F Rizzo, A Weisz, F Belardelli, R Dolcetti, J Dal Col
Although promising, the clinical benefit provided by dendritic cell (DC)-based vaccines is still limited and the choice of the optimal antigen formulation is still an unresolved issue. We have developed a new DC-based vaccination protocol for aggressive and/or refractory lymphomas which combines the unique features of interferon-conditioned DC (IFN-DC) with highly immunogenic tumor cell lysates (TCL) obtained from lymphoma cells undergoing immunogenic cell death. We show that treatment of mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) cell lines with 9-cis-retinoic acid and IFNα (RA/IFNα) induces early membrane exposure of Calreticulin, HSP70 and 90 together with CD47 down-regulation and enhanced HMGB1 secretion...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29146244/extending-antigen-release-from-particulate-vaccines-results-in-enhanced-antitumor-immune-response
#11
Chintan H Kapadia, Shaomin Tian, Jillian L Perry, David Sailer, J Christopher Luft, Joseph M DeSimone
Tumor-specific CD8(+) cytotoxic T lymphocytes (CTLs) play a critical role in an anti-tumor immune response. However, vaccination intended to elicit a potent CD8(+) T cell responses employing tumor-associated peptide antigens, are typically ineffective due to poor immunogenicity. Previously, we engineered a polyethylene glycol (PEG) hydrogel-based subunit vaccine for the delivery of an antigenic peptide and CpG (adjuvant) to elicit potent CTLs. In this study, we further examined the effect of antigen release kinetics on their induced immune responses...
November 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29145441/distinct-t-and-nk-cell-populations-may-serve-as-immune-correlates-of-protection-against-symptomatic-pandemic-influenza-a-h1n1-virus-infection-during-pregnancy
#12
Miloje Savic, Jennifer L Dembinski, Ida Laake, Olav Hungnes, Rebecca Cox, Fredrik Oftung, Lill Trogstad, Siri Mjaaland
Maternal influenza infection during pregnancy is associated with increased risk of morbidity and mortality. However, the link between the anti-influenza immune responses and health-related risks during infection is not well understood. We have analyzed memory T and NK cell mediated immunity (CMI) responses in pandemic influenza A(H1N1)pdm09 (pdm09) virus infected non-vaccinated pregnant women participating in the Norwegian Influenza Pregnancy Cohort (NorFlu). The cohort includes information on immunization, self-reported health and disease status, and biological samples (plasma and PBMC)...
2017: PloS One
https://www.readbyqxmd.com/read/29143375/an-immunoinformatics-approach-to-define-t-cell-epitopes-from-polyketide-and-non-ribosomal-peptide-synthesis-proteins-of-mycobacterium-tuberculosis-as-potential-vaccine-candidates
#13
S Dhivya, V Baskar, S R Kumar, R Sathishkumar
The role of polyketide and non-ribosomal proteins from the class of small molecule metabolism of Mycobacterium tuberculosis is well documented in envelope organization, virulence, and pathogenesis. Consequently, the identification of T cell epitopes from these proteins could serve to define potential antigens for the development of vaccines. Fourty-one proteins from polyketide and non-ribosomal peptide synthesis of small molecule metabolism proteins of M tuberculosis H37Rv were analyzed computationally for the presence of HLA class I binding nanomeric peptides...
November 16, 2017: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/29143114/cancer-vaccine-strategies-translation-from-mice-to-human-clinical-trials
#14
REVIEW
Jay A Berzofsky, Masaki Terabe, Jane B Trepel, Ira Pastan, David F Stroncek, John C Morris, Lauren V Wood
We translated two cancer vaccine strategies from mice into human clinical trials. (1) In preclinical studies on TARP, an antigen expressed in most prostate cancers, we mapped epitopes presented by HLA-A*0201, modified them to increase affinity and immunogenicity in HLA transgenic mice, and induced human T cells that killed human cancer cells ("epitope enhancement"). In a clinical trial, HLA-A2(+) prostate cancer patients with PSA biochemical recurrence (Stage D0) were vaccinated with two peptides either in Montanide-ISA51 or on autologous dendritic cells (DCs)...
November 15, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29141529/experimental-autoimmune-encephalomyelitis-eae-model-of-cynomolgus-macaques-induced-by-recombinant-human-mog1-125-rhmog1-125-protein-and-mog34-56-peptide
#15
Yunxiao Sun, Zhen Peng, Libiao Zhang, Huaqian Wang, Xiangyang He, Xingwen Peng, Qin Zhang, Hui Liu, Junhua Rao, Haifeng Wang, Jie Wu
Experimental autoimmune encephalomyelitis (EAE) induced by self-myelin antigen is a widely used multiple sclerosis (MS) model for preclinical studies of new therapeutics and potential pathogenesis. By comparison with rodent EAE models, EAE models in primates are more similar to MS. Some groups have developed EAE models in primates by using common marmoset (Callithrix jacchus). However, this model has some limitations. EAE in cynomolgus monkey (Macaque fasciculrais) could overcome these limitations. In this study, EAE was induced in cynomolgus monkey by immunizing with the recombinant human myelin oligodendrocyte glycoprotein extracellular domain (1-125) (rhMOG1-125) and a synthetic peptide, representing peptide 34-56 of human myelin oligodendrocyte glycoprotein (MOG34-56) in complete Freund's adjuvant (CFA) and in combination with intravenous injection of pertussis toxin, and subsequent booster immunizations with the same dose of antigen in incomplete Freund's adjuvant (IFA) until the animals developed clinically significant EAE (score≥2)...
November 9, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/29140786/selection-of-an-anticalin%C3%A2-against-the-membrane-form-of-hsp70-via-bacterial-surface-display-and-its-theranostic-application-in-tumour-models
#16
Lars Friedrich, Petra Kornberger, Claudia T Mendler, Gabriele Multhoff, Markus Schwaiger, Arne Skerra
We describe the selection of Anticalins against a common tumour surface antigen, human Hsp70, using functional display on live E. coli cells as fusion with a truncated EspP autotransporter. While found intracellularly in normal cells, Hsp70 is frequently exposed in a membrane-bound state on the surface of tumour cells and, even more pronounced, in metastases or after radiochemotherapy. Employing a recombinant Hsp70 fragment comprising residues 383-548 as target, Anticalins were selected from a naive bacterial library...
November 27, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/29140228/co-factor-independent-phosphoglycerate-mutase-of-leishmania-donovani-modulates-macrophage-signalling-and-promotes-t-cell-repertoires-bearing-epitopes-for-both-mhc-i-and-mhc-ii
#17
Manish K Singh, Fauzia Jamal, Amit K Dubey, Pushkar Shivam, Sarita Kumari, Pushpanjali, Ghufran Ahmed, Manas R Dikhit, S Narayan, V N R DAS, Krishna Pandey, K K Sinha, P DAS, Shubhankar K Singh
Immunoactivation depends upon the antigen potential to modulate T-cell repertoires. The present study has enumerated the effect of 61 kDa recombinant Leishmania donovani co-factor-independent phosphoglycerate mutase (rLd-iPGAM) on mononuclear cells of healthy and treated visceral leishmaniasis subjects as well as on THP-1 cell line. rLd-iPGAM stimulation induced higher expression of interleukin-1β (IL-1β) in the phagocytic cell, its receptor and CD69 on T-cell subsets. These cellular activations resulted in upregulation of host-protective cytokines IL-2, IL-12, IL-17, tumour necrosis factor-α and interferon-γ, and downregulation of IL-4, IL-10 and tumour growth factor-β...
November 15, 2017: Parasitology
https://www.readbyqxmd.com/read/29133420/resident-macrophages-of-pancreatic-islets-have-a-seminal-role-in-the-initiation-of-autoimmune-diabetes-of-nod-mice
#18
Javier A Carrero, Derrick P McCarthy, Stephen T Ferris, Xiaoxiao Wan, Hao Hu, Bernd H Zinselmeyer, Anthony N Vomund, Emil R Unanue
Treatment of C57BL/6 or NOD mice with a monoclonal antibody to the CSF-1 receptor resulted in depletion of the resident macrophages of pancreatic islets of Langerhans that lasted for several weeks. Depletion of macrophages in C57BL/6 mice did not affect multiple parameters of islet function, including glucose response, insulin content, and transcriptional profile. In NOD mice depleted of islet-resident macrophages starting at 3 wk of age, several changes occurred: (i) the early entrance of CD4 T cells and dendritic cells into pancreatic islets was reduced, (ii) presentation of insulin epitopes by dispersed islet cells to T cells was impaired, and (iii) the development of autoimmune diabetes was significantly reduced...
November 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29132960/influenza-derived-peptides-cross-react-with-allergens-and-provide-asthma-protection
#19
Chrysanthi Skevaki, Christoph Hudemann, Mikhail Matrosovich, Christian Möbs, Sinu Paul, Andreas Wachtendorf, Bilal Alashkar Alhamwe, Daniel P Potaczek, Stefanie Hagner, Diethard Gemsa, Holger Garn, Alessandro Sette, Harald Renz
BACKGROUND: The hygiene hypothesis is the leading concept to explain the current asthma epidemic, which is built on the observation that a lack of bacterial contact early in life induces allergic Th2 immune responses. OBJECTIVE: Since little is known about the contribution of respiratory viruses in this context, we evaluated the effect of prior influenza-infection on the development of allergic asthma. METHODS: Mice were infected with influenza and once recovered, subjected to an ovalbumin or house dust mite-induced experimental asthma protocol...
November 10, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29132146/identification-of-unique-neoantigen-qualities-in-long-term-survivors-of-pancreatic-cancer
#20
Vinod P Balachandran, Marta Łuksza, Julia N Zhao, Vladimir Makarov, John Alec Moral, Romain Remark, Brian Herbst, Gokce Askan, Umesh Bhanot, Yasin Senbabaoglu, Daniel K Wells, Charles Ian Ormsby Cary, Olivera Grbovic-Huezo, Marc Attiyeh, Benjamin Medina, Jennifer Zhang, Jennifer Loo, Joseph Saglimbeni, Mohsen Abu-Akeel, Roberta Zappasodi, Nadeem Riaz, Martin Smoragiewicz, Z Larkin Kelley, Olca Basturk, Mithat Gönen, Arnold J Levine, Peter J Allen, Douglas T Fearon, Miriam Merad, Sacha Gnjatic, Christine A Iacobuzio-Donahue, Jedd D Wolchok, Ronald P DeMatteo, Timothy A Chan, Benjamin D Greenbaum, Taha Merghoub, Steven D Leach
Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8(+) T-cell infiltrates, but neither alone, stratified patients with the longest survival...
November 8, 2017: Nature
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