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https://www.readbyqxmd.com/read/28344989/efficient-presentation-of-multiple-endogenous-epitopes-to-both-cd4-and-cd8-diabetogenic-t-cells-for-tolerance
#1
Shamael R Dastagir, Jorge Postigo-Fernandez, Chunliang Xu, James H Stoeckle, Rebuma Firdessa-Fite, Rémi J Creusot
Antigen-specific immunotherapy of type 1 diabetes, typically via delivery of a single native β cell antigen, has had little clinical benefit to date. With increasing evidence that diabetogenic T cells react against multiple β cell antigens, including previously unappreciated neo-antigens that can be emulated by mimotopes, a shift from protein- to epitope-based therapy is warranted. To this end, we aimed to achieve efficient co-presentation of multiple major epitopes targeting both CD4(+) and CD8(+) diabetogenic T cells...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344864/an-immunogenic-wt1-derived-peptide-that-induces-t-cell-response-in-the-context-of-hla-a-02-01-and-hla-a-24-02-molecules
#2
Tao Dao, Tatyana Korontsvit, Victoria Zakhaleva, Casey Jarvis, Patrizia Mondello, Claire Oh, David A Scheinberg
The Wilms' tumor oncogene protein (WT1) is a highly validated tumor antigen for immunotherapy. WT1-targeted immunotherapy has been extensively explored in multiple human trials in various cancers. However, clinical investigations using WT1 epitopes have generally focused on two peptides, HLA-restricted to HLA-A*02:01 or HLA-A*24:02. The goal of this study was to identify new epitopes derived from WT1, to expand the potential use of WT1 as a target of immunotherapy. Using computer-based MHC-binding algorithms and in vitro validation of the T cell responses specific for the identified peptides, we found that a recently identified HLA-A*24:02-binding epitope (239-247), NQMNLGATL (NQM), was also a strong CD8(+) T cell epitope for HLA-A*02:01 molecule...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344577/linear-epitopes-of-paracoccidioides-brasiliensis-and-other-fungal-agents-of-human-systemic-mycoses-as-vaccine-candidates
#3
REVIEW
Luiz R Travassos, Carlos P Taborda
Dimorphic fungi are agents of systemic mycoses associated with significant morbidity and frequent lethality in the Americas. Among the pathogenic species are Paracoccidioides brasiliensis and Paracoccidioides lutzii, which predominate in South America; Histoplasma capsulatum, Coccidioides posadasii, and Coccidioides immitis, and the Sporothrix spp. complex are other important pathogens. Associated with dimorphic fungi other important infections are caused by yeast such as Candida spp. and Cryptococcus spp. or mold such as Aspergillus spp...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28343843/%C3%AE-s1-casein-elucidate-major-t-cell-responses-in-cow-s-milk-allergy
#4
L Diego Archila, Fatima S Khan, Nupur Bhatnagar, David Robinson, Mary L Farrington, William W Kwok
Cow's milk allergy (CMA) is increasing in prevalence, affecting approximately 4% of children. Cow's milk (CM) is a common cause of fatal/ near fatal anaphylactic reactions. Understanding of CM-specific CD4+ T-cells responses to milk allergens should help elucidate the pathological mechanisms of persistent CMA. Milk allergen epitopes specific T-cells were examined in CMA subjects. Frequencies and phenotypes of these T-cells were found to be different between older and younger subjects.
March 23, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28342268/the-susceptible-hla-class-ii-alleles-and-their-presenting-epitope-s-in-goodpasture-s-disease
#5
Li-Jun Xie, Zhao Cui, Fang-Jin Chen, Zhi-Yong Pei, Shui-Yi Hu, Qiu-Hua Gu, Xiao-Yu Jia, Li Zhu, Xu-Jie Zhou, Hong Zhang, Yun-Hua Liao, Lu-Hua Lai, Billy G Hudson, Ming-Hui Zhao
Goodpasture's disease is closely associated with HLA, particularly DRB1*1501. Other susceptible or protective HLA alleles are not clearly elucidated. The presentation models of epitopes by susceptible HLA alleles are also unclear. We genotyped 140 Chinese patients and 599 controls for 4 digits HLA II genes, and extracted the encoding sequences from IMGT/HLA database. T cell epitopes of α3(IV)NC1 were predicted and the structures of DR molecule-peptide-TCR were constructed. We confirmed DRB1*1501 (OR=4.6, P=5...
March 25, 2017: Immunology
https://www.readbyqxmd.com/read/28339124/gliadin-reactive-t-cells-in-italian-children-from-preventcd-cohort-at-high-risk-for-celiac-disease
#6
Alessandra Camarca, Renata Auricchio, Stefania Picascia, Olga Fierro, Mariantonia Maglio, Erasmo Miele, Basilio Malamisura, Luigi Greco, Riccardo Troncone, Carmen Gianfrani
BACKGROUND: Newborns at high risk for celiac disease (CD) were recruited in Italy in the context of the PreventCD Study and closely monitored for CD, from 4 months up to a mean age of 8 years at follow-up. The aim of our study was to investigate intestinal T cell reactivity to gliadin at the first clinical and/or serological signs of CD. METHODS: Gliadin-reactive T cell lines were generated from intestinal biopsies of 19 HLA-DQ2 or HLA-DQ8 positive children. At biopsy, 11 children had a diagnosis of acute CD, two of potential CD, and six were non-celiac controls...
March 24, 2017: Pediatric Allergy and Immunology
https://www.readbyqxmd.com/read/28331179/hyperosmolarity-impedes-the-cross-priming-competence-of-dendritic-cells-in-a-trif-dependent-manner
#7
Zoran V Popovic, Maria Embgenbroich, Federica Chessa, Viola Nordström, Mahnaz Bonrouhi, Thomas Hielscher, Norbert Gretz, Shijun Wang, Daniel Mathow, Thomas Quast, Jan-Gero Schloetel, Waldemar Kolanus, Sven Burgdorf, Hermann-Josef Gröne
Tissue osmolarity varies among different organs and can be considerably increased under pathologic conditions. Hyperosmolarity has been associated with altered stimulatory properties of immune cells, especially macrophages and dendritic cells. We have recently reported that dendritic cells upon exposure to hypertonic stimuli shift their profile towards a macrophage-M2-like phenotype, resulting in attenuated local alloreactivity during acute kidney graft rejection. Here, we examined how hyperosmotic microenvironment affects the cross-priming capacity of dendritic cells...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28331088/bst-2-expression-modulates-small-cd4-mimetic-sensitization-of-hiv-1-infected-cells-to-adcc
#8
Jonathan Richard, Jérémie Prévost, Benjamin von Bredow, Shilei Ding, Nathalie Brassard, Halima Medjahed, Mathieu Coutu, Bruno Melillo, Frédéric Bibollet-Ruche, Beatrice H Hahn, Daniel E Kaufmann, Amos B Smith, Joseph Sodroski, Daniel Sauter, Frank Kirchhoff, Katrina Gee, Stuart J Neil, David T Evans, Andrés Finzi
Antibodies recognizing conserved CD4-induced (CD4i) epitopes on HIV-1 Env and able to mediate antibody-dependent cellular cytotoxicity (ADCC) have been shown to be present in sera from most HIV-1-infected individuals. These antibodies preferentially recognize Env in its CD4-bound conformation. CD4 downregulation by Nef and Vpu dramatically reduces exposure of CD4i HIV-1 Env epitopes and therefore reduce the susceptibility of HIV-1-infected cells to ADCC mediated by HIV+ sera. Importantly, this mechanism of immune evasion can be circumvented with small-molecule CD4-mimetics (CD4mc) which are able to transition Env into the CD4-bound conformation and sensitize HIV-1-infected cells to ADCC mediated by HIV+ sera...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28330372/car-t-cell-therapy-progress-and-prospects
#9
Olivia Wilkins, Allison May Keeler, Terence R Flotte
Lentivirus-mediated transduction of autologous T-cells with a chimeric antigen receptor (CAR) to confer a desired epitope-specificity as a targeted immunotherapy for cancer has been among the first human gene therapy techniques to demonstrate widespread therapeutic efficacy. Other approaches to using gene therapy to enhance anti-tumor immunity have been less specific and less effective. These included amplification, marking, and cytokine transduction of tumor infiltrating lymphocytes (TIL), recombinant virus-based expression of tumor antigens as a tumor vaccine, and transduction of antigen-presenting cells (APCs) with tumor antigens...
March 23, 2017: Human Gene Therapy Methods
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
#10
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/28325910/an-rna-nanoparticle-vaccine-against-zika-virus-elicits-antibody-and-cd8-t-cell-responses-in-a-mouse-model
#11
Jasdave S Chahal, Tao Fang, Andrew W Woodham, Omar F Khan, Jingjing Ling, Daniel G Anderson, Hidde L Ploegh
The Zika virus (ZIKV) outbreak in the Americas and South Pacific poses a significant burden on human health because of ZIKV's neurotropic effects in the course of fetal development. Vaccine candidates against ZIKV are coming online, but immunological tools to study anti-ZIKV responses in preclinical models, particularly T cell responses, remain sparse. We deployed RNA nanoparticle technology to create a vaccine candidate that elicited ZIKV E protein-specific IgG responses in C57BL/6 mice as assayed by ELISA...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28325903/whole-genome-analysis-of-human-papillomavirus-types-16-18-and-58-isolated-from-cervical-precancer-and-cancer-samples-in-chinese-women
#12
Ying Liu, Yaqi Pan, Weijiao Gao, Yang Ke, Zheming Lu
Human papillomavirus (HPV) types 16, 18 and 58 are ranked the top three high-risk HPV types for cervical intraepithelial neoplasia (CIN) and invasive carcinoma. We aimed to evaluate the diversity of HPV16, HPV18, and HPV58 genetic variants by HPV capture technology combined with next generation sequencing. 295, 73, and 148 variations were observed in 51 HPV16, 7 HPV18, and 11 HPV58 genomes, respectively. HPV16 isolates were predominantly of the A variant lineage, and sublineage A4 (Asian) was the most common...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28321221/leishmania-donovani-nucleoside-hydrolase-nh36-domains-induce-t-cell-cytokine-responses-in-human-visceral-leishmaniasis
#13
Micheli Luize Barbosa Santos, Dirlei Nico, Fabrícia Alvisi de Oliveira, Aline Silva Barreto, Iam Palatnik-de-Sousa, Eugenia Carrillo, Javier Moreno, Paula Mello de Luca, Alexandre Morrot, Daniela Santoro Rosa, Marcos Palatnik, Cristiane Bani-Corrêa, Roque Pacheco de Almeida, Clarisa Beatriz Palatnik-de-Sousa
Development of immunoprotection against visceral leishmaniasis (VL) focused on the identification of antigens capable of inducing a Th1 immune response. Alternatively, antigens targeting the CD8 and T-regulatory responses are also relevant in VL pathogenesis and worthy of being included in a preventive human vaccine. We assessed in active and cured patients and VL asymptomatic subjects the clinical signs and cytokine responses to the Leishmania donovani nucleoside hydrolase NH36 antigen and its N-(F1), central (F2) and C-terminal (F3) domains...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28319404/encapsulation-of-an-ep67-conjugated-ctl-peptide-vaccine-in-nanoscale-biodegradable-particles-increases-the-efficacy-of-respiratory-immunization-and-affects-the-magnitude-and-memory-subsets-of-vaccine-generated-mucosal-and-systemic-cd8-t-cells-in-a-diameter
#14
Bala Vamsi Krishna Karuturi, Shailendra B Tallapaka, Pravin Yeapuri, Stephen M Curran, Sam D Sanderson, Joseph A Vetro
The diameter of biodegradable particles used to co-encapsulate immunostimulants and subunit vaccines affects the magnitude of memory CD8(+) T cells generated by systemic immunization. Possible effects on the magnitude of CD8(+) T cells generated by mucosal immunization or memory subsets that potentially correlate more strongly with protection against certain pathogens, however, are unknown. In this study, we conjugated our novel host-derived mucosal immunostimulant, EP67, to the protective MCMV CTL epitope, pp89, through a lysosomal protease-labile double arginine linker (pp89-RR-EP67) and encapsulated in PLGA 50:50 micro- or nanoparticles...
March 20, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28315936/peptide-binding-motifs-of-two-common-equine-class-i-mhc-molecules-in-thoroughbred-horses
#15
Tobias Bergmann, Mikaela Lindvall, Erin Moore, Eugene Moore, John Sidney, Donald Miller, Rebecca L Tallmadge, Paisley T Myers, Stacy A Malaker, Jeffrey Shabanowitz, Nikolaus Osterrieder, Bjoern Peters, Donald F Hunt, Douglas F Antczak, Alessandro Sette
Quantitative peptide-binding motifs of MHC class I alleles provide a valuable tool to efficiently identify putative T cell epitopes. Detailed information on equine MHC class I alleles is still very limited, and to date, only a single equine MHC class I allele, Eqca-1*00101 (ELA-A3 haplotype), has been characterized. The present study extends the number of characterized ELA class I specificities in two additional haplotypes found commonly in the Thoroughbred breed. Accordingly, we here report quantitative binding motifs for the ELA-A2 allele Eqca-16*00101 and the ELA-A9 allele Eqca-1*00201...
March 18, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28315224/an-overview-of-bioinformatics-tools-and-resources-in-allergy
#16
Zhiyan Fu, Jing Lin
The rapidly increasing number of characterized allergens has created huge demands for advanced information storage, retrieval, and analysis. Bioinformatics and machine learning approaches provide useful tools for the study of allergens and epitopes prediction, which greatly complement traditional laboratory techniques. The specific applications mainly include identification of B- and T-cell epitopes, and assessment of allergenicity and cross-reactivity. In order to facilitate the work of clinical and basic researchers who are not familiar with bioinformatics, we review in this chapter the most important databases, bioinformatic tools, and methods with relevance to the study of allergens...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28315223/t-cell-epitope-prediction
#17
George N Konstantinou
An epitope is a part of an immunogenic protein that can be recognized by the immune system. The peptides that can be recognized by the T-cell receptors after a particular antigen has been intracellularly processed, bound to at least one MHC molecule and expressed on the surface of the antigen presenting cell as a MHC-peptide complex, are called a T-cell epitope. Individuals who have at least one MHC molecule able to most avidly bind to allergenic amino acid sequences from an allergen, and at the same time have the appropriate T-cell clone that can recognize this MHC-peptide complex, are expected to be genetically prone to allergic reactions against that allergen...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28315222/tetramer-guided-epitope-mapping-a-rapid-approach-to-identify-hla-restricted-t-cell-epitopes-from-composite-allergens
#18
Luis L Diego Archila, William W Kwok
Tetramer-guided epitope mapping (TGEM) is a technique in immunology that permits the rapid identification of allergenic epitopes through peptide screening procedures utilizing human lymphocyte antigen (HLA) class II tetramers as staining reagents for detection. The identification of allergenic epitopes is a prerequisite for the accurate characterization of allergen-specific CD4(+) T cells without in vitro stimulation. Additionally, these MHC-II/peptide complexes that interact with T-cell receptors (TCR) of pathogenic CD4(+) T cells are compatible with a different number of assays like Intracelullar Cytokine Staining (ICS), and Carboxyfluorescein succinimidyl ester (CFSE) making it a robust technology to study the functionality of allergen-specific CD4(+) T cells...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28315221/t-cell-proliferation-assay-determination-of-immunodominant-t-cell-epitopes-of-food-allergens
#19
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/28314956/evolution-of-mhc-based-technologies-used-for-detection-of-antigen-responsive-t-cells
#20
REVIEW
Amalie Kai Bentzen, Sine Reker Hadrup
T cell-mediated recognition of peptide-major histocompatibility complex (pMHC) class I and II molecules is crucial for the control of intracellular pathogens and cancer, as well as for stimulation and maintenance of efficient cytotoxic responses. Such interactions may also play a role in the development of autoimmune diseases. Novel insights into this mechanism are crucial to understanding disease development and establishing new treatment strategies. MHC multimers have been used for detection of antigen-responsive T cells since the first report by Altman et al...
March 17, 2017: Cancer Immunology, Immunotherapy: CII
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