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https://www.readbyqxmd.com/read/29205500/a-functional-snp-in-the-3-utr-of-tap2-gene-interacts-with-microrna-hsa-mir-1270-to-suppress-the-gene-expression
#1
Bridgett Knox, Yong Wang, Lora J Rogers, Jiekun Xuan, Dianke Yu, Huaijin Guan, Jiwei Chen, Tieliu Shi, Baitang Ning, Susan A Kadlubar
The transporter associated with antigen processing 2 (TAP2) is involved in the development of multidrug resistance and the etiology of immunological diseases. In this study, we investigated whether the expression of TAP2 can be perturbed by single nucleotide polymorphisms (SNPs) located in 3'-untranslated region (3'-UTR) of the gene via interactions with microRNAs. Using a series of in silico assays, we selected the candidate microRNAs (miRNAs) with the potential to interact with functional SNPs of TAP2. The SNP rs241456-located in the 3'-UTR of TAP2-resides in a potential binding site for hsa-miR-1270 and hsa-miR-620...
December 5, 2017: Environmental and Molecular Mutagenesis
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
#2
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/29107940/structure-of-the-human-mhc-i-peptide-loading-complex
#3
Andreas Blees, Dovile Januliene, Tommy Hofmann, Nicole Koller, Carla Schmidt, Simon Trowitzsch, Arne Moeller, Robert Tampé
The peptide-loading complex (PLC) is a transient, multisubunit membrane complex in the endoplasmic reticulum that is essential for establishing a hierarchical immune response. The PLC coordinates peptide translocation into the endoplasmic reticulum with loading and editing of major histocompatibility complex class I (MHC-I) molecules. After final proofreading in the PLC, stable peptide-MHC-I complexes are released to the cell surface to evoke a T-cell response against infected or malignant cells. Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin...
November 6, 2017: Nature
https://www.readbyqxmd.com/read/29091951/downregulation-of-tap1-and-tap2-in-early-stage-breast-cancer
#4
Andrea M Henle, Aziza Nassar, Danell Puglisi-Knutson, Bahaaeldin Youssef, Keith L Knutson
TAP1-TAP2 heterodimeric complexes are recognized as the transporter associated with antigen processing of major histocompatibility complex class I peptides for recognition by tumor-specific cytotoxic T lymphocytes. In this study, we investigated the immunohistochemical expression of TAP1 and TAP2 in 160 patients with breast cancer and correlated their expression levels with clinicopathologic parameters. The median age of the patient cohort was 52.5 years (range, 30-86 years). Both TAP1 and TAP2 immunohistochemical expression levels correlated significantly with breast cancer characteristics (P < ...
2017: PloS One
https://www.readbyqxmd.com/read/29039469/the-association-of-lmp7-and-tap2-gene-polymorphisms-with-treatment-response-to-interferon-ribavirin-in-patients-with-genotype-1-chronic-hepatitis-c
#5
Feng Zang, Yinan Yao, Mei Liu, Haozhi Fan, Ming Yue, Mingzhu Chen, Jie Wang, Rongbin Yu, Peng Huang
Previous studies have highlighted the important role of genes related to antigen presentation in the spontaneous clearance of hepatitis C virus. The present study aimed to explore the association between TAP, LMP and tapasin gene polymorphism and treatment response in chronic hepatitis C virus (CHC) patients. Six single nucleotide polymorphisms in TAP, LMP and tapasin genes were genotyped among 352 Chinese genotype 1 CHC patients with pegylated interferon-α and ribavirin (pegIFN-α/RBV) treatment. There were 232 cases achieving sustained virological response (SVR), which yielded an SVR rate of 65...
October 10, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29020964/il-27-mediates-hla-class-i-up-regulation-which-can-be-inhibited-by-the-il-6-pathway-in-hla-deficient-small-cell-lung-cancer-cells
#6
Grazia Carbotti, Amin Reza Nikpoor, Paola Vacca, Rosaria Gangemi, Chiara Giordano, Francesco Campelli, Silvano Ferrini, Marina Fabbi
BACKGROUND: Recently, immunotherapy with anti-PD-1 antibodies has shown clinical benefit in recurrent Small Cell Lung Cancer (SCLC). Since anti-PD-1 re-activates anti-tumor Cytotoxic T Lymphocyte (CTL) responses, it is crucial to understand the mechanisms regulating HLA class I, and PD-L1 expression in HLA-negative SCLC. Here we addressed the role of IL-27, a cytokine related to both IL-6 and IL-12 families. METHODS: The human SCLC cell lines NCI-N592, -H69, -H146, -H446 and -H82 were treated in vitro with different cytokines (IL-27, IFN-γ, IL-6 or a soluble IL-6R/IL-6 chimera [sIL-6R/IL-6]) at different time points and analyzed for tyrosine-phosphorylated STAT proteins by Western blot, for surface molecule expression by immunofluorescence and FACS analyses or for specific mRNA expression by QRT-PCR...
October 11, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28864056/classification-of-patients-with-sepsis-according-to-blood-genomic-endotype-a-prospective-cohort-study
#7
Brendon P Scicluna, Lonneke A van Vught, Aeilko H Zwinderman, Maryse A Wiewel, Emma E Davenport, Katie L Burnham, Peter Nürnberg, Marcus J Schultz, Janneke Horn, Olaf L Cremer, Marc J Bonten, Charles J Hinds, Hector R Wong, Julian C Knight, Tom van der Poll
BACKGROUND: Host responses during sepsis are highly heterogeneous, which hampers the identification of patients at high risk of mortality and their selection for targeted therapies. In this study, we aimed to identify biologically relevant molecular endotypes in patients with sepsis. METHODS: This was a prospective observational cohort study that included consecutive patients admitted for sepsis to two intensive care units (ICUs) in the Netherlands between Jan 1, 2011, and July 20, 2012 (discovery and first validation cohorts) and patients admitted with sepsis due to community-acquired pneumonia to 29 ICUs in the UK (second validation cohort)...
October 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28721901/psmb8-as-a-candidate-marker-of-responsiveness-to-preoperative-radiation-therapy-in-rectal-cancer-patients
#8
Ye Jin Ha, Ka Hee Tak, Chan Wook Kim, Seon Ae Roh, Eun Kyung Choi, Dong Hyung Cho, Jeong Hwan Kim, Seon Kyu Kim, Seon Young Kim, Yong Sung Kim, Jin Cheon Kim
PURPOSE: The ability to predict individual responsiveness to cancer therapy is urgently needed. This is particularly true for patients with locally advanced rectal cancer (LARC) because a large proportion are resistant to preoperative chemoradiation therapy (CRT). In this study, we sought to identify markers that could predict response by comparing the gene expression profiles of the tumors of patients who received preoperative CRT. METHODS AND MATERIALS: The basal gene expression profiles of tumors from 22 LARC patients who were responders (n=9) and nonresponders (n=13) to preoperative CRT were analyzed using RNA sequencing (RNA-Seq)...
August 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28638726/downregulation-of-antigen-presentation-associated-pathway-proteins-is-linked-to-poor-outcome-in-triple-negative-breast-cancer-patient-tumors
#9
Martin H Pedersen, Brian L Hood, Hans Christian Beck, Thomas P Conrads, Henrik J Ditzel, Rikke Leth-Larsen
Triple-negative breast cancer (TNBC) is a heterogeneous subtype with varying disease outcomes. Tumor-infiltrating lymphocytes (TILs) are frequent in TNBC and have been shown to correlate with outcome, suggesting an immunogenic component in this subtype. However, other factors intrinsic to the cancer cells may also influence outcome. To identify proteins and molecular pathways associated with recurrence in TNBC, 34 formalin-fixed paraffin-embedded (FFPE) primary TNBC tumors were investigated by global proteomic profiling using mass spectrometry...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28536458/epigenetic-priming-restores-the-hla-class-i-antigen-processing-machinery-expression-in-merkel-cell-carcinoma
#10
Cathrin Ritter, Kaiji Fan, Annette Paschen, Sine Reker Hardrup, Soldano Ferrone, Paul Nghiem, Selma Ugurel, David Schrama, Jürgen C Becker
Merkel cell carcinoma (MCC) is a rare and aggressive, yet highly immunogenic skin cancer. The latter is due to its viral or UV-associated carcinogenesis. For tumor progression MCC has to escape the host's immuno-surveillance, e.g. by loss of HLA class-I expression. Indeed, a reduced HLA class-I expression was observed in MCC tumor tissues and MCC cell lines. This reduced HLA class-I surface expression is caused by an impaired expression of key components of the antigen processing machinery (APM), including LMP2 and LMP7 as well as TAP1 and TAP2...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28503748/cigarette-smoking-induces-only-marginal-changes-in-sperm-dna-methylation-levels-of-patients-undergoing-intracytoplasmic-sperm-injection-treatment
#11
Y Al Khaled, S Tierling, M Laqqan, C Lo Porto, M E Hammadeh
DNA methylation plays important roles in genome stability and regulation of gene expression. This study was designed to determine the influence of cigarette smoking on sperm DNA methylation. From a genome-wide survey on sperm samples, differentially methylated target CpGs should be selected and subjected to local deep bisulphite sequencing. Obtained methylation data are compared to sperm parameters and (ICSI) outcome. Similar to pilot study, samples were subjected to Infinium 450K BeadChip arrays to identify alterations in sperm DNA methylation between smokers and nonsmokers males...
May 14, 2017: Andrologia
https://www.readbyqxmd.com/read/28405734/genetic-association-between-tap1-and-tap2-polymorphisms-and-ankylosing-spondylitis-a-systematic-review-and-meta-analysis
#12
Yufeng Qian, Genlin Wang, Feng Xue, Lianghui Chen, Yan Wang, Liang Tang, Huilin Yang
OBJECTIVES: Ankylosing spondylitis (AS) is a chronic inflammatory joint disease. The transporter associated with antigen processing (TAP) has been identified to play an important role in immune response as well as the HLA-associated diseases. The aim of our meta-analysis was to investigate the contribution of TAP (TAP1 and TAP2) polymorphisms to the risk of AS. METHODS: Meta-analyses were performed between 2 polymorphisms in TAP1 (TAP1-333, -637) and 3 polymorphisms in TAP2 (TAP2-379, -565, and -665) and AS...
August 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28254693/tlr4-md2-specific-peptides-stalled-in%C3%A2-vivo-lps-induced-immune-exacerbation
#13
Seolhee Park, Hyeon-Jun Shin, Masaud Shah, Hey-Young Cho, Muhammad Ayaz Anwar, Asma Achek, Hyuk-Kwon Kwon, Byugsung Lee, Tae Hyeon Yoo, Sangdun Choi
Negative regulation of Toll-like receptor-4 (TLR4) is anticipated to control the pathogen-induced exaggerated immune response. However, effective TLR4 antagonists with scarce off-target effects are yet to be developed. To fill this void, we sought to design small peptide-inhibitors of the TLR4/MD2-LPS interaction. Here we report novel TLR4-antagonistic peptides (TAP), identified through phage display, endowed with the LPS-induced proinflammation inhibition, and confirmed in mice. TAPs-attributed TLR4-antagonism were initially evaluated through NF-κB inhibition in HEK-blue hTLR4 and RAW264...
February 20, 2017: Biomaterials
https://www.readbyqxmd.com/read/27997612/signatures-of-crested-ibis-mhc-revealed-by-recombination-screening-and-short-reads-assembly-strategy
#14
Liao Chang, Shiyang He, Danqing Mao, Yuanhong Liu, Zijun Xiong, Dongke Fu, Bo Li, Shuguang Wei, Xun Xu, Shengbin Li, Hui Yuan
Whole-genome shotgun (WGS) sequencing has become a routine method in genome research over the past decade. However, the assembly of highly polymorphic regions in WGS projects remains a challenge, especially for large genomes. Employing BAC library constructing, PCR screening and Sanger sequencing, traditional strategy is laborious and expensive, which hampers research on polymorphic genomic regions. As one of the most highly polymorphic regions, the major histocompatibility complex (MHC) plays a central role in the adaptive immunity of all jawed vertebrates...
2016: PloS One
https://www.readbyqxmd.com/read/27861817/a-novel-spontaneous-mutation-in-the-tap2-gene-unravels-its-role-in-macrophage-survival
#15
Antonio Lapenna, Ibrahim Omar, Michael Berger
We report a new mouse strain with a single point mutation in the type 2 transporter associated with antigen processing (TAP2). This strain randomly arose in one of our C57BL/6J mouse colonies and was initially discovered because of the lack of CD8(+) T cells in the periphery. Following our observation, we subsequently revealed a lack of cell surface MHC-I expression, derived from TAP2 protein deficiency. Our strain, named eightless, has a C to T substitution in exon 5 resulting in a glutamine to stop codon substitution at position 285 in the TAP2 protein...
April 2017: Immunology
https://www.readbyqxmd.com/read/27745831/an-ancient-fecundability-associated-polymorphism-switches-a-repressor-into-an-enhancer-of-endometrial-tap2-expression
#16
Katelyn M Mika, Vincent J Lynch
Variation in female reproductive traits, such as fertility, fecundity, and fecundability, is heritable in humans, but identifying and functionally characterizing genetic variants associated with these traits has been challenging. Here, we explore the functional significance and evolutionary history of a T/C polymorphism of SNP rs2071473, which we have previously shown is an eQTL for TAP2 and significantly associated with fecundability (time to pregnancy). We replicated the association between the rs2071473 genotype and TAP2 expression by using GTEx data and demonstrated that TAP2 is expressed by decidual stromal cells at the maternal-fetal interface...
November 3, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27698133/epstein-barr-virus-micrornas-reduce-immune-surveillance-by-virus-specific-cd8-t-cells
#17
Manuel Albanese, Takanobu Tagawa, Mickaël Bouvet, Liridona Maliqi, Dominik Lutter, Jonathan Hoser, Maximilian Hastreiter, Mitch Hayes, Bill Sugden, Larissa Martin, Andreas Moosmann, Wolfgang Hammerschmidt
Infection with Epstein-Barr virus (EBV) affects most humans worldwide and persists life-long in the presence of robust virus-specific T-cell responses. In both immunocompromised and some immunocompetent people, EBV causes several cancers and lymphoproliferative diseases. EBV transforms B cells in vitro and encodes at least 44 microRNAs (miRNAs), most of which are expressed in EBV-transformed B cells, but their functions are largely unknown. Recently, we showed that EBV miRNAs inhibit CD4(+) T-cell responses to infected B cells by targeting IL-12, MHC class II, and lysosomal proteases...
October 18, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27651309/bptf-depletion-enhances-t-cell-mediated-antitumor-immunity
#18
Kimberly Mayes, Suehyb G Alkhatib, Kristen Peterson, Aiman Alhazmi, Carolyn Song, Vivian Chan, Tana Blevins, Mark Roberts, Catherine I Dumur, Xiang-Yang Wang, Joseph W Landry
Genetic studies in fruit flies have implicated the chromatin remodeling complex nucleosome remodeling factor (NURF) in immunity, but it has yet to be studied in mammals. Here we show that its targeting in mice enhances antitumor immunity in two syngeneic models of cancer. NURF was disabled by silencing of bromodomain PHD-finger containing transcription factor (BPTF), the largest and essential subunit of NURF. We found that both CD8(+) and CD4(+) T cells were necessary for enhanced antitumor activity, with elevated numbers of activated CD8(+) T cells observed in BPTF-deficient tumors...
November 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27493218/alternative-haplotypes-of-antigen-processing-genes-in-zebrafish-diverged-early-in-vertebrate-evolution
#19
Sean C McConnell, Kyle M Hernandez, Dustin J Wcisel, Ross N Kettleborough, Derek L Stemple, Jeffrey A Yoder, Jorge Andrade, Jill L O de Jong
Antigen processing and presentation genes found within the MHC are among the most highly polymorphic genes of vertebrate genomes, providing populations with diverse immune responses to a wide array of pathogens. Here, we describe transcriptome, exome, and whole-genome sequencing of clonal zebrafish, uncovering the most extensive diversity within the antigen processing and presentation genes of any species yet examined. Our CG2 clonal zebrafish assembly provides genomic context within a remarkably divergent haplotype of the core MHC region on chromosome 19 for six expressed genes not found in the zebrafish reference genome: mhc1uga, proteasome-β 9b (psmb9b), psmb8f, and previously unknown genes psmb13b, tap2d, and tap2e We identify ancient lineages for Psmb13 within a proteasome branch previously thought to be monomorphic and provide evidence of substantial lineage diversity within each of three major trifurcations of catalytic-type proteasome subunits in vertebrates: Psmb5/Psmb8/Psmb11, Psmb6/Psmb9/Psmb12, and Psmb7/Psmb10/Psmb13...
August 23, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27447835/expression-quantitative-trait-locus-mapping-studies-in-mid-secretory-phase-endometrial-cells-identifies-hla-f-and-tap2-as-fecundability-associated-genes
#20
Courtney K Burrows, Gülüm Kosova, Catherine Herman, Kristen Patterson, Katherine E Hartmann, Digna R Velez Edwards, Mary D Stephenson, Vincent J Lynch, Carole Ober
Fertility traits in humans are heritable, however, little is known about the genes that influence reproductive outcomes or the genetic variants that contribute to differences in these traits between individuals, particularly women. To address this gap in knowledge, we performed an unbiased genome-wide expression quantitative trait locus (eQTL) mapping study to identify common regulatory (expression) single nucleotide polymorphisms (eSNPs) in mid-secretory endometrium. We identified 423 cis-eQTLs for 132 genes that were significant at a false discovery rate (FDR) of 1%...
July 2016: PLoS Genetics
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