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https://www.readbyqxmd.com/read/28635644/pd-1-pd-l1-blockade-therapy-for-tumors-with-downregulated-mhc-class-i-expression
#1
REVIEW
Michal Šmahel
The therapy of different advanced-stage malignancies with monoclonal antibodies blocking programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) signaling has had an impressive long-lasting effect in a portion of patients, but in most cases, this therapy was not successful, or a secondary resistance developed. To enhance its efficacy in treated patients, predictive biomarkers are searched for and various combination treatments are intensively investigated. As the downregulation of major histocompatibility complex (MHC) class I molecules is one of the most frequent mechanisms of tumor escape from the host's immunity, it should be considered in PD-1/PD-L1 checkpoint inhibition...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28632753/mait-cells-launch-a-rapid-robust-and-distinct-hyperinflammatory-response-to-bacterial-superantigens-and-quickly-acquire-an-anergic-phenotype-that-impedes-their-cognate-antimicrobial-function-defining-a-novel-mechanism-of-superantigen-induced-immunopathology
#2
Christopher R Shaler, Joshua Choi, Patrick T Rudak, Arash Memarnejadian, Peter A Szabo, Mauro E Tun-Abraham, Jamie Rossjohn, Alexandra J Corbett, James McCluskey, John K McCormick, Olivier Lantz, Roberto Hernandez-Alejandro, S M Mansour Haeryfar
Superantigens (SAgs) are potent exotoxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They target a large fraction of T cell pools to set in motion a "cytokine storm" with severe and sometimes life-threatening consequences typically encountered in toxic shock syndrome (TSS). Given the rapidity with which TSS develops, designing timely and truly targeted therapies for this syndrome requires identification of key mediators of the cytokine storm's initial wave. Equally important, early host responses to SAgs can be accompanied or followed by a state of immunosuppression, which in turn jeopardizes the host's ability to combat and clear infections...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28630682/overexpressed-prame-is-a-potential-immunotherapy-target-in-sarcoma-subtypes
#3
Jason Roszik, Wei-Lien Wang, John A Livingston, Christina L Roland, Vinod Ravi, Cassian Yee, Patrick Hwu, Andrew Futreal, Alexander J Lazar, Shreyaskumar R Patel, Anthony P Conley
BACKGROUND: PRAME (preferentially expressed antigen in melanoma), a member of the cancer-testis antigen family, has been shown to have increased expression in solid tumors, including sarcoma, and PRAME-specific therapies are currently in development for other cancers such as melanoma. METHODS: To map the landscape of PRAME expression in sarcoma, we used publicly available data from The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE) projects and determined which sarcoma subtypes and subsets are associated with increased PRAME expression...
2017: Clinical Sarcoma Research
https://www.readbyqxmd.com/read/28628857/identification-of-b-and-t-cell-epitope-based-peptide-vaccine-from-igf-1-receptor-in-breast-cancer
#4
Manijeh Mahdavi, Violaine Moreau, Majid Kheirollahi
The insulin-like growth factor-1 receptor (IGF-1R) plays a key role in proliferation, growth, differentiation, and development of several human malignancies including breast and pancreatic adenocarcinoma. IGF-1R targeted immunotherapeutic approaches are particularly attractive, as they may potentially elicit even stronger antitumor responses than traditional targeted approaches. Cancer peptide vaccines can produce immunologic responses against cancer cells by triggering helper T cell (Th) or cytotoxic T cells (CTL) in association with Major Histocompatibility Complex (MHC) class I or II molecules on the cell surface of antigen presenting cells...
June 8, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28628013/modulation-of-antitumor-immune-response-in-mouse-prostate-cancer-model
#5
N Mitskevich, T Tsertsvadze, K Mchedlishvili, K Matchavariani, G Guruli
Aim of study - prostate cancer is second most common cancer in men worldwide, and fifth leading cause of death from cancer in men (6.6% of the total men deaths). Unfortunately, once cancer spreads outside of prostate, it becomes incurable. Androgen deprivation can provide some relief, but resistance will develop eventually, and at that time no effective treatment options are left to the patient. Therefore, the search of alternative treatment modalities is paramount. In this article we evaluated the role of epigenetic modifier 5-azacitidine (5-AzaC) and immunomodulator - Lenalidomide and their possible impact on the immune response in the murine prostate cancer model...
May 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28624424/fusaric-acid-fa-protects-heart-failure-induced-by-isoproterenol-isp-in-mice-through-fibrosis-prevention-via-tgf-%C3%AE-1-smads-and-pi3k-akt-signaling-pathways
#6
Xin Li, Zhou-Long Zhang, Hui-Fen Wang
Fusaric acid (FA) is a novel compound derived from a class of nicotinic acid derivatives, exhibiting activity against cancers. However, its role in regulating cardiac injury is limited. Our study was aimed to investigate the role and the underlying molecular mechanism of FA in heart fibrosis and hypertrophy. Isoproterenol (ISP) was used to induce cardiac fibrosis and hypertrophy in vitro and in vivo. FA administration ameliorated hypertrophy by reducing atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β -myosin heavy chain (β-MHC) in vitro and in vivo...
June 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28623659/immune-activation-of-platelets-in-response-to-serial-phlebotomy-in-pigtailed-macaques-macaca-nemestrina
#7
Kelly A Metcalf Pate, Meghan S Vermillion, Claire E Lyons, Kevin M Najarro, Robert J Adams
Serial phlebotomy is a common sampling practice for repeated-measures studies in biomedical research. In NHP, the effect ofserial blood collection on RBC parameters has been characterized, but the effects on platelet parameters and other aspects of thehemogram have not been well studied. We sought to characterize the circulating platelet phenotype throughout the course of 7serial phlebotomies spanning 30 d in pigtailed macaques (Macaca nemestrina). Phlebotomy was performed on 23 animals at days0, 2, 4, 7, 10, 21, and 30 to quantify the circulating platelet count and markers of both hemostatic and immune platelet activation...
June 16, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28623393/limited-mhc-class-i-intron-2-repertoire-variation-in-bonobos
#8
Natasja G de Groot, Corrine M C Heijmans, Philippe Helsen, Nel Otting, Zjef Pereboom, Jeroen M G Stevens, Ronald E Bontrop
Common chimpanzees (Pan troglodytes) experienced a selective sweep, probably caused by a SIV-like virus, which targeted their MHC class I repertoire. Based on MHC class I intron 2 data analyses, this selective sweep took place about 2-3 million years ago. As a consequence, common chimpanzees have a skewed MHC class I repertoire that is enriched for allotypes that are able to recognise conserved regions of the SIV proteome. The bonobo (Pan paniscus) shared an ancestor with common chimpanzees approximately 1...
June 16, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28623392/mhc-class-i-diversity-in-chimpanzees-and-bonobos
#9
Vincent Maibach, Jörg B Hans, Christina Hvilsom, Tomas Marques-Bonet, Linda Vigilant
Major histocompatibility complex (MHC) class I genes are critically involved in the defense against intracellular pathogens. MHC diversity comparisons among samples of closely related taxa may reveal traces of past or ongoing selective processes. The bonobo and chimpanzee are the closest living evolutionary relatives of humans and last shared a common ancestor some 1 mya. However, little is known concerning MHC class I diversity in bonobos or in central chimpanzees, the most numerous and genetically diverse chimpanzee subspecies...
June 16, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28623356/high-risk-human-papillomavirus-e7-alters-host-dna-methylome-and-represses-hla-e-expression-in-human-keratinocytes
#10
Louis Cicchini, Rachel Z Blumhagen, Joseph A Westrich, Mallory E Myers, Cody J Warren, Charlotte Siska, David Raben, Katerina J Kechris, Dohun Pyeon
Human papillomavirus (HPV) infection distinctly alters methylation patterns in HPV-associated cancer. We have recently reported that HPV E7-dependent promoter hypermethylation leads to downregulation of the chemokine CXCL14 and suppression of antitumor immune responses. To investigate the extent of gene expression dysregulated by HPV E7-induced DNA methylation, we analyzed parallel global gene expression and DNA methylation using normal immortalized keratinocyte lines, NIKS, NIKS-16, NIKS-18, and NIKS-16∆E7...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28615415/cutting-edge-the-aging-immune-system-reveals-the-biological-impact-of-direct-antigen-presentation-on-cd8-t-cell-responses
#11
Jennifer L Uhrlaub, Megan J Smithey, Janko Nikolich-Žugich
The vertebrate immune system uses multiple, sometimes redundant, mechanisms to contain pathogenic microorganisms that are always evolving to evade host defenses. Thus, the cowpox virus (CPXV) uses genes encoding CPXV12 and CPXV203 to prevent direct MHC class I presentation of viral peptides by infected cells. However, CD8 T cells are effectively primed against CPXV by cross-presentation of viral Ags in young mice. Old mice accumulate defects in both CD8 T cell activation and cross-presentation. Using a double-deletion mutant (∆12∆203) of CPXV, we show that direct priming of CD8 T cells in old mice yields superior recall responses, establishing a key contribution of this mechanism to host antipoxvirus responses and enhancing our fundamental understanding of how viral manipulation of direct presentation impacts pathogenesis...
June 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28615212/conserved-v%C3%AE-1-binding-geometry-in-a-setting-of-locus-disparate-phla-recognition-by-%C3%AE-%C3%AE-%C3%AE-tcrs-insight-into-recognition-of-hiv-peptides-by-tcr
#12
Yi Shi, Ai Kawana-Tachikawa, Feng Gao, Jianxun Qi, Chuansheng Liu, Jia Gao, Hao Cheng, Takamasa Ueno, Aikichi Iwamoto, George F Gao
Given a limited set of TCR V genes which are used to create TCRs that are reactive to different ligands, such as MHC class I, MHC class II and MHC-like proteins (for example, MIC molecules and CD1 molecules), the Vδ1 segment can be rearranged with Dδ-Jδ-Cδ or Jα-Cα segments, to form classical γδTCR or uncommon αβTCR using a Vδ1 segment (δ/αβTCR). Here we have determined two complex structures of the δ/αβTCRs (S19-2 and TU55) bound to different locus-disparate MHCIs with HIV peptides (HLA-A*2402-Nef138-10 and HLA-B*3501-Pol448-9)...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28615208/deficiency-of-the-nod-like-receptor-nlrc5-results-in-decreased-cd8-t-cell-function-and-impaired-viral-clearance
#13
Christopher R Lupfer, Kate L Stokes, Teneema Kuriakose, Thirumala-Devi Kanneganti
Pathogen recognition receptors are vital components of the immune system. Engagement of these receptors is important not only for instigation of innate immune responses to invading pathogens but also for initiating the adaptive immune response. Members of the NOD-like receptor (NLR) family of pathogen recognition receptors have important roles in orchestrating this response. The NLR family member, NLRC5 regulates major histocompatibility complex class I (MHC-I) expression during various types of infections, but its role in immunity to influenza A virus (IAV) is not well studied...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28606812/novel-ctl-epitopes-identified-through-a-y-pestis-proteome-wide-analysis-in-the-search-for-vaccine-candidates-against-plague
#14
Anat Zvi, Shahar Rotem, Ayelet Zauberman, Uri Elia, Moshe Aftalion, Erez Bar-Haim, Emanuelle Mamroud, Ofer Cohen
The causative agent of Plague, Yersinia pestis, is a highly virulent pathogen and a potential bioweapon. Depending on the route of infection, two prevalent occurrences of the disease are known, bubonic and pneumonic. The latter has a high fatality rate. In the absence of a licensed vaccine, intense efforts to develop a safe and efficacious vaccine have been conducted, and humoral-driven subunit vaccines containing the F1 and LcrV antigens are currently under clinical trials. It is well known that a cellular immune response might have an essential additive value to immunity and protection against Y...
June 9, 2017: Vaccine
https://www.readbyqxmd.com/read/28605050/the-abl-1-kinase-is-dispensable-for-nk-cell-inhibitory-signaling-and-is-not-involved-in-murine-nk-cell-education
#15
S Ganesan, T L Thanh, N Kadri, B J Chambers, S Meinke, P Brodin, E Vivier, D M Wetzel, A J Koleske, P Höglund
Natural killer (NK) cell responsiveness in the mouse is determined in an education process guided by inhibitory Ly49 and NKG2A receptors binding to MHC class I molecules. It has been proposed that inhibitory signaling in human NK cells involves Abl-1 (c-Abl)-mediated phosphorylation of Crk, lowering NK cell function via disruption of a signaling complex including C3G and c-Cbl, suggesting that NK cell education might involve c-Abl. Mice deficient in c-Abl expression specifically in murine NK cells displayed normal inhibitory and activating receptor repertoires...
June 12, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28596769/c1-complex-an-adaptable-proteolytic-module-for-complement-and-non-complement-functions
#16
REVIEW
Jinhua Lu, Uday Kishore
Complement C1 is the defining component of the classical pathway. Within the C1qC1r2C1s2 complex, C1q functions as a molecular scaffold for C1r2C1s2 and C1q binding to its ligands activates these two serine proteases. The classic C1q ligands are antigen-bound antibodies and activated C1s cleaves C4 and C2 to initiate the complement cascade. Recent studies suggest broad C1 functions beyond the complement system. C1q binds to the Frizzled receptors to activate C1s, which cleaves lipoprotein receptor-related protein 6 to trigger aging-associated Wnt receptor signaling...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28595953/inhalation-of-a-racemic-mixture-r-s-linalool-by-rats-experiencing-restraint-stress-alters-neuropeptide-and-mhc-class-i-gene-expression-in-the-hypothalamus
#17
Kazushi Yoshida, Naoto Yamamoto, Satoshi Fujiwara, Asuka Kamei, Keiko Abe, Akio Nakamura
Some odorants have physiological and psychological effects on organisms. However, little is known about the effects of inhaling them, particularly on the central nervous system. Using DNA microarray analysis, we obtained gene expression profiles of the hypothalamus from restraint stressed rats exposed to racemic (R,S)-linalool. Hierarchical clustering across all probe sets showed that this inhalation of (R,S)-linalool influenced the expression levels of a wide range of genes in the hypothalamus. A comparison of transcription levels revealed that the inhalation of (R,S)-linalool restored the expression of 560 stress-induced probe sets to a normal status...
June 6, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28592828/a-highly-conserved-sequence-of-the-viral-tap-inhibitor-icp47-is-required-for-freezing-of-the-peptide-transport-cycle
#18
Tony Matschulla, Richard Berry, Carolin Gerke, Marius Döring, Julia Busch, Jennifer Paijo, Ulrich Kalinke, Frank Momburg, Hartmut Hengel, Anne Halenius
The transporter associated with antigen processing (TAP) translocates antigenic peptides into the endoplasmic reticulum (ER) lumen for loading onto MHC class I molecules. This is a key step in the control of viral infections through CD8+ T-cells. The herpes simplex virus type-1 encodes an 88 amino acid long species-specific TAP inhibitor, ICP47, that functions as a high affinity competitor for the peptide binding site on TAP. It has previously been suggested that the inhibitory function of ICP47 resides within the N-terminal region (residues 1-35)...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28592531/use-of-a-recombinant-gamma-2-herpesvirus-vaccine-vector-against-dengue-virus-in-rhesus-monkeys
#19
Georg F Bischof, Diogo M Magnani, Michael Ricciardi, Young C Shin, Aline Domingues, Varian K Bailey, Lucas Gonzalez-Nieto, Eva G Rakasz, David I Watkins, Ronald C Desrosiers
Research on vaccine approaches that can provide long-term protection against dengue virus infection is needed. Here we describe the construction, immunogenicity, and preliminary information on protective capacity of recombinant, replication-competent rhesus monkey rhadinovirus (RRV), a persisting herpesvirus. One RRV construct expressed the non-structural protein 5 (NS5) while a second recombinant expressed a soluble variant of the E protein (E85) of dengue virus 2 (DENV2). Four rhesus macaques received a single vaccination with a mixture of both recombinant RRVs and were subsequently challenged 19 weeks later with 1 x 10(5) PFU of DENV2...
June 7, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28585770/mining-the-proteome-of-leishmania-donovani-for-the-development-of-novel-mhc-class-i-restricted-epitope-for-the-control-of-visceral-leishmaniasis
#20
Manas R Dikhit, Vijay Mahantesh, Akhilesh Kumar, Ajay Amit, Budheswar Dehury, Yangya Prasad Nathsharma, Md Yousuf Ansari, Vahab Ali, Roshan Kamal Topno, Vnr Das, Krishna Pandey, Ganesh Chandra Sahoo, Sanjiva Bimal, Pradeep Das
Although, the precise host defence mechanism(s) is not completely understood, T cell-mediated immune responses is believed to play a pivotal role in controlling parasite infection. Here we target the stage dependent over expressed gene. Here, the consensus based computational approach was adopted for the screening of potential major histocompatibility complex class I restricted epitopes. Based on the computational analysis and previously published report, a set 19 antigenic proteins derived from Leishmania donovani were screened for further characterization as vaccine candidates...
June 6, 2017: Journal of Cellular Biochemistry
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