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https://www.readbyqxmd.com/read/28537924/genetic-defects-of-the-irf1-mediated-major-histocompatibility-complex-class-i-antigen-presentation-pathway-occur-prevalently-in-the-jak2-gene-in-non-small-cell-lung-cancer
#1
Tao Shen, Zhengming Chen, Zhizhuang Joe Zhao, Jie Wu
Recognition of major histocompatibility complex (MHC) class I antigens on tumor cells by cytotoxic T cells is involved in T cell-mediated tumor immune surveillance and immune checkpoint therapy. The interferon-γ (IFNγ)-IRF1 signaling pathway regulates MHC class I antigen presentation. To examine genetic defects of the IFNγ-IRF1 pathway in non-small cell lung cancer (NSCLC), we analyzed The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LuAd) and lung squamous cell carcinoma (LuSc) data. Loss-of-function (LOF) genetic alterations of the IFNγ-IRF1 pathway genes (IFNGR1, IFNGR2, JAK1, JAK2, STAT1, IRF1) were found in 64 (6...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28534224/characterization-of-mhc-class-i-in-a-long-distance-migratory-wader-the-icelandic-black-tailed-godwit
#2
Sara Pardal, Anna Drews, José A Alves, Jaime A Ramos, Helena Westerdahl
The major histocompatibility complex (MHC) encodes proteins that are central for antigen presentation and pathogen elimination. MHC class I (MHC-I) genes have attracted a great deal of interest among researchers in ecology and evolution and have been partly characterized in a wide range of bird species. So far, the main focus has been on species within the bird orders Galliformes and Passeriformes, while Charadriiformes remain vastly underrepresented with only two species studied to date. These two Charadriiformes species exhibit striking differences in MHC-I characteristics and MHC-I diversity...
May 23, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28528220/properties-of-the-tapasin-homologue-tapbpr
#3
REVIEW
Andreas Neerincx, Louise H Boyle
The presentation of antigenic peptides by MHC class I molecules plays a vital role in generating T cell responses against infection and cancer. Over the last two decades the central role of tapasin as a peptide editor that influences the loading and optimisation of peptides onto MHC class I molecules has been extensively characterised. Recently, it has become evident that the tapasin-related protein, TAPBPR, functions as a second peptide editor which influences the peptides displayed by MHC class I molecules...
May 18, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28528219/the-ongoing-saga-of-the-mechanism-s-of-mhc-class-i-restricted-cross-presentation
#4
Jeff E Grotzke, Debrup Sengupta, Qiao Lu, Peter Cresswell
Cross-presentation is an MHC-I antigen processing pathway that results in the presentation of peptides from exogenous viral, bacterial, parasitic, and tumor antigens and ultimately leads to priming of naïve CD8(+) T cells. This process involves several cellular compartments and multiple components. Successful generation of MHC-I-peptide complexes requires that these components act together in a coordinated fashion. We discuss recent findings on the source of MHC-I, the role of the TAP transporter, the importance of intracellular trafficking events, mechanisms of antigen access the cytosol, and how innate immune signals can affect presentation, with an emphasis on how these pathways compare to conventional antigen presentation and how they correlate with existing data...
May 18, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28521800/immunogenicity-and-immunomodulatory-effects-of-the-human-chondrocytes-hchonj
#5
Chae-Lyul Lim, Yeon-Ju Lee, Jong-Ho Cho, Heonsik Choi, Bumsup Lee, Myung Chul Lee, Sujeong Kim
BACKGROUND: Invossa™ (TissueGene-C) is a cell and gene therapy for osteoarthritis. It is composed of primary human chondrocytes (hChonJ cells) and irradiated human chondrocytes modified to express TGF-β1 (hChonJb#7 cells). The hChonJ cells were isolated from a polydactyly donor, and TGF-β1 cDNA was delivered to the cells, generating hChonJb#7 cells. Since the cells are allogeneic, the concern of immune response against cells has been raised. In this study, we investigated the immunogenicity of allogenic human chondrocyte, hChonJ cells...
May 18, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28518056/functionally-diverse-human-t-cells-recognize-non-microbial-antigens-presented-by-mr1
#6
Marco Lepore, Artem Kalinichenko, Salvatore Calogero, Pavanish Kumar, Bhairav Paleja, Mathias Schmaler, Vipin Narang, Francesca Zolezzi, Michael Poidinger, Lucia Mori, Gennaro De Libero
MHC class I-related molecule MR1 presents riboflavin- and folate-related metabolites to mucosal-associated invariant T cells, but it is unknown whether MR1 can present alternative antigens to other T cell lineages. In healthy individuals we identified MR1-restricted T cells (named MR1T cells) displaying diverse TCRs and reacting to MR1-expressing cells in the absence of microbial ligands. Analysis of MR1T cell clones revealed specificity for distinct cell-derived antigens and alternative transcriptional strategies for metabolic programming, cell cycle control and functional polarization following antigen stimulation...
May 18, 2017: ELife
https://www.readbyqxmd.com/read/28515281/cxcl4-exposure-potentiates-tlr-driven-polarization-of-human-monocyte-derived-dendritic-cells-and-increases-stimulation-of-t-cells
#7
Sandra C Silva-Cardoso, Alsya J Affandi, Lotte Spel, Marta Cossu, Joel A G van Roon, Marianne Boes, Timothy R D J Radstake
Chemokines have been shown to play immune-modulatory functions unrelated to steering cell migration. CXCL4 is a chemokine abundantly produced by activated platelets and immune cells. Increased levels of circulating CXCL4 are associated with immune-mediated conditions, including systemic sclerosis. Considering the central role of dendritic cells (DCs) in immune activation, in this article we addressed the effect of CXCL4 on the phenotype and function of monocyte-derived DCs (moDCs). To this end, we compared innate and adaptive immune responses of moDCs with those that were differentiated in the presence of CXCL4...
May 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28508465/proteomics-show-antigen-presentation-processes-in-human-immune-cells-after-as03-h5n1-vaccination
#8
Allison C Galassie, Johannes B Goll, Parimal Samir, Travis L Jensen, Kristen L Hoek, Leigh M Howard, Tara M Allos, Xinnan Niu, Laura E Gordy, C Buddy Creech, Heather Hill, Sebastian Joyce, Kathryn M Edwards, Andrew J Link
Adjuvants enhance immunity elicited by vaccines through mechanisms that are poorly understood. Using a systems biology approach, we investigated temporal protein expression changes in five primary human immune cell populations: neutrophils, monocytes, natural killer (NK) cells, T-cells, and B-cells after administration of either an Adjuvant System 03 (AS03)-adjuvanted or unadjuvanted split-virus H5N1 influenza vaccine. Monocytes demonstrated the strongest differential signal between vaccine groups. On day 3 post-vaccination, several antigen presentation-related pathways, including MHC class I-mediated antigen processing and presentation, were enriched in monocytes and neutrophils and expression of HLA Class I proteins was increased in the AS03 group...
May 15, 2017: Proteomics
https://www.readbyqxmd.com/read/28507791/the-mutational-status-of-p53-can-influence-its-recognition-by-human-t-cells
#9
Katerina Shamalov, Shlomo N Levy, Miryam Horovitz-Fried, Cyrille J Cohen
p53 was reported to be an attractive immunotherapy target because it is mutated in approximately half of human cancers, resulting in its inactivation and often accumulation in tumor cells. Peptides derived from p53 are presented by class I MHC molecules and may act as tumor-associated epitopes which could be targeted by p53-specific T cells. Interestingly, it was recently shown that there is a lack of significant correlation between p53 expression levels in tumors and their recognition by p53-TCR transduced T cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28505602/unusual-antigen-presentation-offers-new-insight-into-hiv-vaccine-design
#10
REVIEW
Andrew J McMichael, Louis J Picker
Recent findings with a rhesus monkey cytomegalovirus based simian immunodeficiency virus vaccine have identified strong CD8+ T cell responses that are restricted by MHC-E. Also mycobacteria specific CD8+ T cells, that are MHC-E restricted, have been identified. MHC-E therefore can present a wide range of epitope peptides to CD8+ T cells, alongside its well defined role in presenting a conserved MHC-class I signal peptide to the NKG2A/C-CD94 receptor on natural killer cells. Here we explore the antigen processing pathways involved in these atypical T cell responses...
May 12, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28501972/genetic-variation-of-major-histocompatibility-complex-genes-in-the-endangered-red-crowned-crane
#11
Takuya Akiyama, Tetsuo I Kohyama, Chizuko Nishida, Manabu Onuma, Kunikazu Momose, Ryuichi Masuda
Populations that have drastically decreased in the past often have low genetic variation, which may increase the risk of extinction. The genes of major histocompatibility complex (MHC) play an important role in the adaptive immune response of jawed vertebrates. Maintenance of adaptive genetic diversity such as that of MHC genes is important for wildlife conservation. Here, we determined genotypes of exon 3 of MHC class IA genes (MHCIA) and exon 2 of MHC class IIB genes (MHCIIB) to evaluate genetic variation of the endangered red-crowned crane population on Hokkaido Island, Japan, which experienced severe population decline in the past...
May 14, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28496946/alpha-alumina-nanoparticle-conjugation-to-cysteine-peptidase-a-and-b-an-efficient-method-for-autophagy-induction
#12
Fatemeh Beyzay, Ahmad Zavaran Hosseini, Sara Soudi
BACKGROUND: Autophagy as a cellular pathway facilitates several immune responses against infection. It also eliminates invading pathogens through transferring content between the cytosol and the lysosomal vesicles and contributes to the cross-presentation of exogenous antigens to T lymphocytes via MHC class I pathway. Autophagy induction is one of the main targets for new drugs and future vaccine formulations. Nanoparticles are one of the candidates for autophagy induction. Cysteine Peptidase A (CPA) and Cysteine Peptidase B (CPB) are two members of papain family (Clan CA, family C1) enzyme that have been considered as a virulence factor of Leishmania (L...
April 2017: Avicenna Journal of Medical Biotechnology
https://www.readbyqxmd.com/read/28495615/a-novel-function-of-tlr4-in-mediating-the-immunomodulatory-effect-of-benzanthrone-an-environmental-pollutant
#13
Prachi Tewari, Payal Mandal, Ruchi Roy, Somya Asthana, Premendra D Dwivedi, Mukul Das, Anurag Tripathi
Our prior studies have reported that Benzanthrone (BA) manifests inflammatory responses in the spleen of Balb/c mice. The present investigation was carried out to study the impact of BA on macrophages, which are the primary scavenger cells in the body that act as a connecting link between innate and adaptive immunity. Parenteral administration of BA (daily for one week) to mice resulted in enhanced levels of nitric oxide (NO) and overexpression of inflammatory markers (COX-2, MMP-9 and PGE-2) in macrophages; however the level of MHC class-I and MHC class-II receptors were down regulated...
May 8, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28495139/high-yield-primary-microglial-cultures-using-granulocyte-macrophage-colony-stimulating-factor-from-embryonic-murine-cerebral-cortical-tissue
#14
Adam C Yu, Sarah E Neil, Jacqueline A Quandt
BACKGROUND: Microglia play vital roles in neurotrophic support and modulating immune or inflammatory responses to pathogens or damage/stressors during disease. This study describes the ability to establish large numbers of microglia from embryonic tissues with the addition of granulocyte-macrophage stimulating factor (GM-CSF) and characterizes their similarities to adult microglia examined ex vivo as well as their responses to inflammatory mediators. METHOD: Microglia were seeded from a primary embryonic mixed cortical suspension with the addition of GM-CSF...
June 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28494867/essential-roles-of-satb1-in-specifying-t-lymphocyte-subsets
#15
Kiyokazu Kakugawa, Satoshi Kojo, Hirokazu Tanaka, Wooseok Seo, Takaho A Endo, Yohko Kitagawa, Sawako Muroi, Mari Tenno, Nighat Yasmin, Yoshinori Kohwi, Shimon Sakaguchi, Terumi Kowhi-Shigematsu, Ichiro Taniuchi
T cell receptor (TCR) signaling by MHC class I and II induces thymocytes to acquire cytotoxic and helper fates via the induction of Runx3 and ThPOK transcription factors, respectively. The mechanisms by which TCR signaling is translated into transcriptional programs for each cell fate remain elusive. Here, we show that, in post-selection thymocytes, a genome organizer, SATB1, activates genes for lineage-specifying factors, including ThPOK, Runx3, CD4, CD8, and Treg factor Foxp3, via regulating enhancers in these genes in a locus-specific manner...
May 9, 2017: Cell Reports
https://www.readbyqxmd.com/read/28494200/a-new-therapeutic-potential-for-cancers-one-car-with-2-different-engines
#16
Abdolkarim Sheikhi, Abdollah Jafarzadeh
Tumor cells escape from immune recognition by several mechanisms such as down-regulating of MHC class I molecules, losing of tumor antigens, etc. The purpose of cancer immunotherapy is to robust or reconstruct the capacity of the immune system to recognize and kill tumor cells by overwhelming the mechanisms by which tumors escape the immune response. One of the novel immunotherapeutic strategies were used to potentiate NK- and T cell functions is chimeric antigen receptor (CAR). CARs are composed of an antigen-binding domain of a molecule such as an antibody (that binds to a tumor associated antigens expressed on the surface of tumor cells) and an intracellular T cell activation domain...
May 11, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28491873/b-cd8-t-cell-interactions-in-the-anti-idiotypic-response-against-a-self-antibody
#17
Darel Martínez, Amaury Pupo, Lianet Cabrera, Judith Raymond, Nichol E Holodick, Ana María Hernández
P3 is a murine, germline, IgM mAb that recognizes N-glycolylated gangliosides and other self-antigens. This antibody is able to induce an anti-idiotypic IgG response and B-T idiotypic cascade, even in the absence of any adjuvant or carrier protein. P3 mAb immunization induces the expression of activation markers in a significant percentage of B-1a cells in vivo. Interestingly, transfer of both B-1a and B-2 to BALB/Xid mice was required to recover anti-P3 IgG response in this model. In fact, P3 mAb activated B-2 cells, in vitro, inducing secretion of IFN-γ and IL-4, although this activation was not detected ex vivo...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28490583/structural-definition-of-duck-mhc-class-i-molecules-that-might-explain-efficient-ctl-immunity-against-influenza-a-virus
#18
Yanan Wu, Junya Wang, Shuhua Fan, Rong Chen, Yanjie Liu, Jianhua Zhang, Hongyu Yuan, Ruiying Liang, Nianzhi Zhang, Chun Xia
A single dominantly expressed allele of the major histocompatibility complex class I (MHC I) may be responsible for the duck's high tolerance to the highly pathogenic (HP) influenza A virus (IAV) compared to the chicken's lower tolerance. In this study, the crystal structures of duck MHC I (Anpl-UAA*01) and duck β2m with two peptides from the H5N1 strains were determined, respectively. Two remarkable features were found to distinguish the Anpl-UAA*01 complex from other known MHC I structures. A disulfide bond formed by Cys(95) and Cys(112) and connecting the β5 and β6 sheets at the bottom of peptide binding groove (PBG) in Anpl-UAA*01 complex, which can enhance IAV peptides binding, was identified...
May 10, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28489338/regulatory-t-cells-promote-natural-killer-cell-education-in-mixed-chimeras
#19
Benedikt Mahr, Nina Pilat, Svenja Maschke, Nicolas Granofszky, Christoph Schwarz, Lukas Unger, Karin Hock, Andreas M Farkas, Christoph Klaus, Heinz Regele, Thomas Wekerle
Therapeutic administration of regulatory T cells (Tregs) leads to engraftment of conventional doses of allogeneic bone marrow (BM) in non-irradiated recipient mice conditioned with costimulation blockade and mTOR inhibition. The mode of action responsible for this Treg effect is poorly understood but may encompass the control of costimulation blockade-resistant natural killer (NK) cells. We show that transient NK cell depletion at the time of BM transplantation (BMT) led to BM engraftment and persistent chimerism without Treg transfer, but failed to induce skin graft tolerance...
May 10, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28489076/hla-dp-84gly-constitutively-presents-endogenous-peptides-generated-by-the-class-i-antigen-processing-pathway
#20
Yuki Yamashita, Mark Anczurowski, Munehide Nakatsugawa, Makito Tanaka, Yuki Kagoya, Ankit Sinha, Kenji Chamoto, Toshiki Ochi, Tingxi Guo, Kayoko Saso, Marcus O Butler, Mark D Minden, Thomas Kislinger, Naoto Hirano
Classical antigen processing leads to the presentation of antigenic peptides derived from endogenous and exogenous sources for MHC class I and class II molecules, respectively. Here we show that, unlike other class II molecules, prevalent HLA-DP molecules with β-chains encoding Gly84 (DP(84Gly)) constitutively present endogenous peptides. DP(84Gly) does not bind invariant chain (Ii) via the class II-associated invariant chain peptide (CLIP) region, nor does it present CLIP. However, Ii does facilitate the transport of DP(84Gly) from the endoplasmic reticulum (ER) to the endosomal/lysosomal pathway by transiently binding DP(84Gly) via a non-CLIP region(s) in a pH-sensitive manner...
May 10, 2017: Nature Communications
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