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https://www.readbyqxmd.com/read/28923982/emerging-concepts-in-tcr-specificity-rationalizing-and-maybe-predicting-outcomes
#1
REVIEW
Nishant K Singh, Timothy P Riley, Sarah Catherine B Baker, Tyler Borrman, Zhiping Weng, Brian M Baker
T cell specificity emerges from a myriad of processes, ranging from the biological pathways that control T cell signaling to the structural and physical mechanisms that influence how TCRs bind peptides and MHC proteins. Of these processes, the binding specificity of the TCR is a key component. However, TCR specificity is enigmatic: TCRs are at once specific but also cross-reactive. Although long appreciated, this duality continues to puzzle immunologists and has implications for the development of TCR-based therapeutics...
October 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28923896/experimental-and-theoretical-approaches-to-investigate-the-immunogenicity-of-taenia-solium-derived-ke7-antigen
#2
Raúl J Bobes, José Navarrete-Perea, Adrián Ochoa-Leyva, Víctor Hugo Anaya, Marisela Hernández, Jacquelynne Cervantes-Torres, Karel Estrada, Filiberto Sánchez-Lopez, Xavier Soberón, Gabriela Rosas, Cáris Maroni Nunes, Martín García-Varela, Rogerio Rafael Sotelo-Mundo, Alonso Alexis López-Zavala, Goar Gevorkian, Gonzalo Acero, Juan P Laclette, Gladis Fragoso, Edda Sciutto
Taenia solium cysticercosis, a parasitic disease that affects human health in various regions of the world, is preventable by vaccination. Both the 97-amino-acid-long KETc7 peptide and its carboxyl-terminal, 18-amino-acid-long sequence (GK-1) are found in Taenia crassiceps Both peptides, with proven protective capacity against cysticercosis, are part of the highly conserved, cestode-native, 264-amino-acid long protein KE7. KE7 belongs to a ubiquitously distributed family of proteins associated to membrane processes and may participate in several vital cell pathways...
September 18, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28923084/viral-based-vaccine-tg4010-induces-broadening-of-specific-immune-response-and-improves-outcome-in-advanced-nsclc
#3
Caroline Tosch, Bérangère Bastien, Luc Barraud, Benoit Grellier, Virginie Nourtier, Murielle Gantzer, Jean Marc Limacher, Eric Quemeneur, Kaïdre Bendjama, Xavier Préville
BACKGROUND: Advanced non-small cell lung cancer patients receiving TG4010, a therapeutic viral vaccine encoding human Mucin 1 and interleukin-2 in addition to standard chemotherapy, displayed longer overall survival in comparison to that of patients treated with standard chemotherapy alone. Our study intended to establish the association between overall survival and vaccine-induced T cell responses against tumor associated antigens (TAA) targeted by the vaccine. METHOD: The TIME trial was a placebo-controlled, randomized phase II study aimed at assessing efficacy of TG4010 with chemotherapy in NSCLC...
September 19, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28922374/fractional-laser-exposure-induces-neutrophil-infiltration-n1-phenotype-into-the-tumor-and-stimulates-systemic-anti-tumor-immune-response
#4
Masayoshi Kawakubo, Shadmehr Demehri, Dieter Manstein
BACKGROUND: Ablative fractional photothermolysis (aFP) using a CO2 laser generates multiple small diameter tissue lesions within the irradiation field. aFP is commonly used for a wide variety of dermatological indications, including treatment of photodamaged skin and dyschromia, drug delivery and modification of scars due to acne, surgical procedures and burns. In this study we explore the utility of aFP for treating oncological indications, including induction of local tumor regression and inducing anti-tumor immunity, which is in marked contrast to current indications of aFP...
2017: PloS One
https://www.readbyqxmd.com/read/28919988/identification-of-a-hla-a-0201-restricted-immunogenic-epitope-from-the-universal-tumor-antigen-depdc1
#5
Anna Tosi, Silvia Dalla Santa, Elisa Cappuzzello, Carolina Marotta, Dawid Walerich, Giannino Del Sal, Paola Zanovello, Roberta Sommaggio, Antonio Rosato
The identification of universal tumor-specific antigens shared between multiple patients and/or multiple tumors is of great importance to overcome the practical limitations of personalized cancer immunotherapy. Recent studies support the involvement of DEPDC1 in many aspects of cancer traits, such as cell proliferation, resistance to induction of apoptosis and cell invasion, suggesting that it may play key roles in the oncogenic process. In this study, we report that DEPDC1 expression is upregulated in most types of human tumors, and closely linked to a poorer prognosis; therefore, it might be regarded as a novel universal oncoantigen potentially suitable for targeting many different cancers...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919551/identification-of-potential-antigens-from-non-classically-secreted-proteins-and-designing-novel-multitope-peptide-vaccine-candidate-against-brucella-melitensis-through-reverse-vaccinology-and-immunoinformatics-approach
#6
Udayakumar S Vishnu, Jagadesan Sankarasubramanian, Paramasamy Gunasekaran, Jeyaprakash Rajendhran
Brucella melitensis is an intracellular pathogen resides in the professional and non-professional phagocytes of the host, causing zoonotic disease brucellosis. The stealthy nature of the Brucella makes it's highly pathogenic, and it is hard to eliminate the bacteria completely from the infected host. Hitherto, no licensed vaccines are available for human brucellosis. In this study, we identified potential antigens for vaccine development from non-classically secreted proteins through reverse vaccinology approach...
September 14, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28917539/hemagglutinin-specific-cd4-t-cell-responses-following-2009-ph1n1-inactivated-split-vaccine-inoculation-in-humans
#7
Shuguang Tan, Shihong Zhang, Bin Wu, Yingze Zhao, Wei Zhang, Min Han, Ying Wu, Guoli Shi, Yingxia Liu, Jinghua Yan, Guizhen Wu, Hua Wang, George F Gao, Fengcai Zhu, William J Liu
Influenza A virus remains a major threat to public health, and the inactivated split-virus vaccine is the most prevalent vaccine used worldwide. However, our knowledge about cellular immune responses to the inactivated influenza virus vaccine and its correlation with humoral responses are yet limited, which has restricted our understanding of the vaccine's protective mechanisms. Herein, in two clinical trials, T-cell responses specific for both previously identified human leucocyte antigen (HLA)-I-restricted epitopes from influenza virus and hemagglutinin (HA) protein were longitudinally investigated before, during, and after a two-dose vaccination with the inactivated 2009 pandemic H1N1 (2009-pH1N1) vaccine...
September 13, 2017: Vaccine
https://www.readbyqxmd.com/read/28914200/development-of-peptide-vaccines-in-dengue
#8
Kavita Reginald, Yanqi Chan, Magdalena Plebanski, Chit Laa Poh
Dengue is one of the most important arboviral infection worldwide, infecting up to 390 million people and causing 25,000 deaths annually. Although a licensed dengue vaccine is available, it is not efficacious against dengue serotypes that infect people living in South East Asia, where dengue is an endemic disease. Hence, there is an urgent need to develop an efficient dengue vaccine for this region. Data from different clinical trials indicate that a successful dengue vaccine must elicit both neutralizing antibodies and cell mediated immunity...
September 13, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28914198/pemtb-a-database-of-mhc-antigenic-peptide-of-mycobacterium-tuberculosis
#9
Qamar Zia, Asim Azhar, Shadab Ahmad, Mohammad Afsar, Ziaul Hasan, Mohammad Owais, Mahfooz Alam, Shabab Akbar, Magdah Ganash, Ghulam Md Ashraf, Swaleha Zubair, Gjumrakch Aliev
BACKGROUND: For design of a subunit vaccine for tuberculosis, identification of antigenic T-cell epitope is of utmost importance. Several MHC prediction server are available that can accurately predict antigenic peptide of variable lengths. However, peptides predicted from one server not necessarily are predicted form another server, thus creating a confusing situation for scientists to choose a best epitope. METHOD: Keeping the above problem in mind, we developed a comprehensive database of peptides of Mycobacterial proteins...
September 14, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28912827/development-of-taqman-probes-targeting-the-four-major-celiac-disease-epitopes-found-in-%C3%AE-gliadin-sequences-of-spelt-triticum-aestivum-ssp-spelta-and-bread-wheat-triticum-aestivum-ssp-aestivum
#10
Benjamin Dubois, Pierre Bertin, Yordan Muhovski, Emmanuelle Escarnot, Dominique Mingeot
BACKGROUND: Celiac disease (CD) is caused by specific sequences of gluten proteins found in cereals such as bread wheat (Triticum aestivum ssp. aestivum) and spelt (T. aestivum ssp. spelta). Among them, the α-gliadins display the highest immunogenicity, with four T-cell stimulatory epitopes. The toxicity of each epitope sequence can be reduced or even suppressed according to the allelic form of each sequence. One way to address the CD problem would be to make use of this allelic variability in breeding programs to develop safe varieties, but tools to track the presence of toxic epitopes are required...
2017: Plant Methods
https://www.readbyqxmd.com/read/28912369/customized-viral-immunotherapy-for-hpv-associated-cancer
#11
Matthew J Atherton, Kyle B Stephenson, Jonathan Pol, Fuan Wang, Charles Lefebvre, David F Stojdl, Jake K Nikota, Anna Dvorkin-Gheva, Andrew Nguyen, Lan Chen, Stephanie Johnson-Obaseki, Patrick J Villeneuve, Jean-Simon Diallo, Jim Dimitroulakos, Yonghong Wan, Brian D Lichty
The viral transforming proteins E6 and E7 make human papilloma virus positive (HPV+) malignancies an attractive target for cancer immunotherapy. However, therapeutic vaccination exerts limited efficacy in the setting of advanced disease. We designed a strategy to induce substantial specific immune responses against multiple epitopes of E6 and E7 proteins based on an attenuated transgene from HPV serotypes 16 and 18 that is incorporated into MG1-Maraba virotherapy (MG1-E6E7). Mutations introduced to the transgene abrogate the ability of E6 and E7 to perturb p53 and retinoblastoma, respectively, while maintaining the ability to invoke tumor-specific, multi-functional CD8+ T-cell responses...
September 14, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28912108/leptospira-borgpetersenii-hybrid-leucine-rich-repeat-protein-cloning-and-expression-immunogenic-identification-and-molecular-docking-evaluation
#12
Tepyuda Sritrakul, Supachai Nitipan, Worawidh Wajjwalku, Anchalee La-Ard, Chattip Suphatpahirapol, Wimol Petkarnjanapong, Boonsong Ongphiphadhanakul, Siriwan Prapong
Leptospirosis is an important zoonotic disease, and the major outbreak of this disease in Thailand in 1999 was due largely to the Leptospira borgpetersenii serovar Sejroe. Identification of the leucine-rich repeat (LRR) LBJ_2271 protein containing immunogenic epitopes and the discovery of the LBJ_2271 ortholog in Leptospira serovar Sejroe, KU_Sej_R21_2271, led to further studies of the antigenic immune properties of KU_Sej_LRR_2271. The recombinant hybrid (rh) protein was created and expressed from a hybrid PCR fragment of KU_Sej_R21_2271 fused with DNA encoding the LBJ_2271 signal sequence for targeting protein as a membrane-anchoring protein...
September 11, 2017: Journal of Microbiological Methods
https://www.readbyqxmd.com/read/28910565/an-in-vivo-study-adjuvant-activity-of-poly-n-vinyl-2-pyrrolidone-co-acrylic-acid-on-immune-responses-against-melanoma-synthetic-peptide
#13
Kadriye Kızılbey, Banu Mansuroğlu, Serap Derman, Zeynep Mustafaeva Akdeste
INTRODUCTION: Peptides have been studied as an important class of components in medicine to control many major diseases with vaccination. Polymers as adjuvants are capable of enhancing the vaccine potential against various diseases by improving the delivery of antigens, and they reduce the booster doses of vaccines. In brief, polymers are promising candidates for peptide-based vaccine delivery platforms. The purpose of the present study was to create a possible alternative approach in the treatment of malignant melanoma and/or to prevent metastasis of melanoma...
September 14, 2017: Bioengineered
https://www.readbyqxmd.com/read/28904177/limited-proteolysis-as-a-tool-to-probe-the-tertiary-conformation-of-dysferlin-and-structural-consequences-of-patient-missense-variant-l344p
#14
Natalie Woolger, Adam Bournazos, Reece A Sophocleous, Frances J Evesson, Angela Lek, Birgit Driemer, R Bryan Sutton, Sandra T Cooper
Dysferlin is a large transmembrane protein that plays a key role in cell membrane repair, and underlies a recessive form of inherited muscular dystrophy. Dysferlinopathy is characterized by absence or marked reduction of dysferlin protein, with 43% of reported pathogenic variants being missense variants that span the length of the dysferlin protein. The unique structure of dysferlin, with seven tandem C2-domains separated by linkers, suggest dysferlin may dynamically associate with phospholipid membranes in response to Ca2+ signaling...
September 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28903331/the-antigenic-identity-of-human-class-i-mhc-phosphopeptides-is-critically-dependent-upon-phosphorylation-status
#15
Fiyaz Mohammed, Daniel H Stones, Angela L Zarling, Carrie R Willcox, Jeffrey Shabanowitz, Kara L Cummings, Donald F Hunt, Mark Cobbold, Victor H Engelhard, Benjamin E Willcox
Dysregulated post-translational modification provides a source of altered self-antigens that can stimulate immune responses in autoimmunity, inflammation, and cancer. In recent years, phosphorylated peptides have emerged as a group of tumour-associated antigens presented by MHC molecules and recognised by T cells, and represent promising candidates for cancer immunotherapy. However, the impact of phosphorylation on the antigenic identity of phosphopeptide epitopes is unclear. Here we examined this by determining structures of MHC-bound phosphopeptides bearing canonical position 4-phosphorylations in the presence and absence of their phosphate moiety, and examining phosphopeptide recognition by the T cell receptor (TCR)...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28902877/purification-and-characterization-of-a-highly-specific-polyclonal-antibody-against-human-extracellular-signal-regulated-kinase-8-and-its-detection-in-lung-cancer
#16
Na-Li Cai, Andy T Y Lau, Fei-Yuan Yu, Dan-Dan Wu, Li-Juan Dai, Hai-Ying Mo, Chang-Min Lin, Yan-Ming Xu
Extracellular signal-regulated kinase 8 (ERK8), proposed as a novel potential therapeutic target for cancer, has been implicated in cell transformation, apoptosis, the protection of genomic integrity, and autophagy. To facilitate ERK8 research, a highly specific anti-ERK8 antibody is needed. In this article, we use the Immune Epitope Database and Analysis Resource online tool to predict B-cell epitopes of human ERK8 protein, and choose a 28 aa-peptide sequence to generate the GST-ERK8(28aa) fusion protein as the antigen for developing polyclonal antibody against ERK8...
2017: PloS One
https://www.readbyqxmd.com/read/28895362/-cd133-epitope-vaccine-with-gp96-as-adjuvant-elicits-an-antitumor-t-cell-response-against-leukemia
#17
Shuo Wang, Hongxia Fan, Yang Li, Huaguo Zheng, Xin Li, Changfei Li, Lizhao Chen, Ying Ju, Songdong Meng
Cancer stem cells are currently under intensive investigation due to their capabilities for tumor initiation, self-renewal, and resistance to chemotherapy. CD133 is implicated in stemness and the malignancy of tumor cells. Here, we explored heat shock protein gp96 adjuvanted CD133 epitope vaccine against leukemia. We screened and identified three H2-Kd-restricted cytotoxic T lymphocyte (CTL) epitopes derived from CD133, CD133₄₁₉₋₄₂₈, CD133₇₀₂₋₇₁₀ and CD133₇₆₀₋₇₆₉. The immunogenicity and antitumor activity of the epitope vaccine using heat shock protein gp96 as adjuvant were further determined in CD133⁺ leukemia xenograft mice...
June 25, 2017: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
https://www.readbyqxmd.com/read/28894200/soluble-hla-associated-peptide-from-psf1-has-a-cancer-vaccine-potency
#18
Mari Yoshida, Yukichi Ishioka, Takamasa Ozawa, Hirohisa Okuyama, Motofumi Iguchi, Takeshi Ota, Takaomi Ito, Morio Nagira, Atsushi Morita, Hidekazu Tanaka, Hisamichi Naito, Hiroyasu Kidoya, Nobuyuki Takakura
Partner of sld five 1 (PSF1) is an evolutionary conserved DNA replication factor involved in DNA replication in lower species, which is strongly expressed in normal stem cell populations and progenitor cell populations. Recently, we have investigated PSF1 functions in cancer cells and found that PSF1 plays a significant role in tumour growth. These findings provide initial evidence for the potential of PSF1 as a therapeutic target. Here, we reveal that PSF1 contains an immunogenic epitope suitable for an antitumour vaccine...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28894111/induction-of-high-titred-non-neutralising-antibodies-by-self-adjuvanting-peptide-epitopes-derived-from-the-respiratory-syncytial-virus-fusion-protein
#19
Noushin Jaberolansar, Keith J Chappell, Daniel Watterson, Imogen M Bermingham, Istvan Toth, Paul R Young, Mariusz Skwarczynski
Respiratory syncytial virus (RSV) causes severe lower respiratory tract illness in infants and young children. The significant morbidity and mortality rates associated with RSV infection make an effective RSV vaccine development a priority. Two neutralising antibody binding sites, Ø and II, located on the pre-fusion RSV F glycoprotein are prime candidates for epitope-focused vaccine design. We report on a vaccine strategy that utilises a lipid core peptide (LCP) delivery system with self-adjuvanting properties in conjunction with either the antigenic site Ø or II (B cell epitopes) along with PADRE as a T helper cell epitope...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28893290/evasion-of-adaptive-immunity-by-hiv-through-the-action-of-host-apobec3g-f-enzymes
#20
REVIEW
Michael Grant, Mani Larijani
APOBEC3G (A3G) and APOBEC3F (A3F) are DNA-mutating enzymes expressed in T cells, dendritic cells and macrophages. A3G/F have been considered innate immune host factors, based on reports that they lethally mutate the HIV genome in vitro. In vivo, A3G/F effectiveness is limited by viral proteins, entrapment in inactive complexes and filtration of mutations during viral life cycle. We hypothesized that the impact of sub-lethal A3G/F action could extend beyond the realm of innate immunity confined to the cytoplasm of infected cells...
September 12, 2017: AIDS Research and Therapy
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