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https://www.readbyqxmd.com/read/27861817/a-novel-spontaneous-mutation-in-the-tap2-gene-unravels-its-role-in-macrophage-survival
#1
Antonio Lapenna, Ibrahim Omar, Michael Berger
Here 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 colony and was initially discovered due to lack of CD8(+) T cells in the periphery. Following our observation, we subsequently revealed a lack of cell surface major histocompatibility complex (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...
November 18, 2016: Immunology
https://www.readbyqxmd.com/read/27745831/an-ancient-fecundability-associated-polymorphism-switches-a-repressor-into-an-enhancer-of-endometrial-tap2-expression
#2
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
#3
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
#4
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
#5
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
#6
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
https://www.readbyqxmd.com/read/27445359/genome-wide-association-studies-and-gene-expression-profiles-of-rheumatoid-arthritis-an-analysis
#7
X Xiao, J Hao, Y Wen, W Wang, X Guo, F Zhang
OBJECTIVES: The molecular mechanism of rheumatoid arthritis (RA) remains elusive. We conducted a protein-protein interaction network-based integrative analysis of genome-wide association studies (GWAS) and gene expression profiles of RA. METHODS: We first performed a dense search of RA-associated gene modules by integrating a large GWAS meta-analysis dataset (containing 5539 RA patients and 20 169 healthy controls), protein interaction network and gene expression profiles of RA synovium and peripheral blood mononuclear cells (PBMCs)...
July 2016: Bone & Joint Research
https://www.readbyqxmd.com/read/27430716/the-minor-mhc-class-i-gene-uda-of-ducks-is-regulated-by-let-7-microrna
#8
Wing Fuk Chan, Julie A Parks-Dely, Brad G Magor, Katharine E Magor
In many nonmammalian vertebrates, the genomic organization of the MHC class I region leads to biased expression of a single classical MHC class I gene coevolving with TAP transporters, whereas class I genes are poorly expressed. This contrasts to the three codominantly expressed classical MHC class I genes in humans and mice. In a sequenced haplotype from White Pekin duck, Anas platyrhynchos, there is one predominantly expressed MHC class I, UAA, although they have five MHC class I genes in the complex, arranged TAP1-TAP2-UAA-UBA-UCA-UDA-UEA The UAA gene, situated proximal to the TAP2 gene, is expressed at levels 10-fold greater than that of another expressed gene, UDA...
August 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27342841/extensive-allelic-diversity-of-mhc-class-i-in-wild-mallard-ducks
#9
Ximena Fleming-Canepa, Shawna M Jensen, Christine M Mesa, Laura Diaz-Satizabal, Alexa J Roth, Julie A Parks-Dely, Debra A Moon, Janet P Wong, Danyel Evseev, Desolie A Gossen, David G Tetrault, Katharine E Magor
MHC class I is critically involved in defense against viruses, and diversity from polygeny and polymorphism contributes to the breadth of the immune response and health of the population. In this article, we examine MHC class I diversity in wild mallard ducks, the natural host and reservoir of influenza A viruses. We previously showed domestic ducks predominantly use UAA, one of five MHC class I genes, but whether biased expression is also true for wild mallards is unknown. Using RT-PCR from blood, we examined expressed MHC class I alleles from 38 wild mallards (Anas platyrhynchos) and identified 61 unique alleles, typically 1 or 2 expressed alleles in each individual...
August 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27325005/association-of-polymorphisms-of-the-transporter-associated-with-antigen-processing-tap2-gene-with-pulmonary-tuberculosis-in-an-elderly-japanese-population
#10
Kaung Si Thu, Noriko Sato, Shinobu Ikeda, Makiko Naka-Mieno, Tomio Arai, Seijiro Mori, Motoji Sawabe, Masaaki Muramatsu, Masashi Tanaka
The transporter associated with antigen processing 2 (TAP2) gene is involved in the immunological response to tuberculosis (TB) infection. Variations in the TAP2 gene have been associated with TB infection in small population studies in India, Columbia, and Korea. We investigated the association of TAP2 polymorphisms with TB susceptibility in an elderly Japanese population. We analyzed samples from consecutive autopsy cases (n = 1850) registered in the Japanese Geriatric SNP Research database. TB was diagnosed pathologically by TB granuloma on autopsy samples...
August 2016: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/27183594/characterization-of-the-antigen-processing-machinery-and-endogenous-peptide-presentation-of-a-bat-mhc-class-i-molecule
#11
James W Wynne, Amanda P Woon, Nadine L Dudek, Nathan P Croft, Justin H J Ng, Michelle L Baker, Lin-Fa Wang, Anthony W Purcell
Bats are a major reservoir of emerging and re-emerging infectious diseases, including severe acute respiratory syndrome-like coronaviruses, henipaviruses, and Ebola virus. Although highly pathogenic to their spillover hosts, bats harbor these viruses, and a large number of other viruses, with little or no clinical signs of disease. How bats asymptomatically coexist with these viruses is unknown. In particular, little is known about bat adaptive immunity, and the presence of functional MHC molecules is mostly inferred from recently described genomes...
June 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27098790/association-analysis-of-proteasome-subunits-and-transporter-associated-with-antigen-processing-on-chinese-patients-with-parkinson-s-disease
#12
Ming-Shu Mo, Wei Huang, Cong-Cong Sun, Li-Min Zhang, Luan Cen, You-Sheng Xiao, Guo-Fei Li, Xin-Ling Yang, Shao-Gang Qu, Ping-Yi Xu
BACKGROUND: Proteasome subunits (PSMB) and transporter associated with antigen processing (TAP) loci are located in the human leukocyte antigen (HLA) Class II region play important roles in immune response and protein degradation in neurodegenerative diseases. This study aimed to explore the association between single nucleotide polymorphisms (SNPs) of PSMB and TAP and Parkinson's disease (PD). METHODS: A case-control study was conducted by genotyping SNPs in PSMB8, PSMB9, TAP1, and TAP2 genes in the Chinese population...
May 5, 2016: Chinese Medical Journal
https://www.readbyqxmd.com/read/26996113/association-of-tap1-and-tap2-gene-polymorphisms-with-susceptibility-to-pulmonary-tuberculosis
#13
Mohammad Naderi, Mohammad Hashemi, Shadi Amininia
TAP1 and TAP2 genes encode heterodimeric molecule involved in endogenous antigen processing. The present study was undertaken to find out the possible association between TAP1 and TAP2 polymorphisms and risk of pulmonary tuberculosis (PTB) in a sample of Iranian population. Polymorphisms of TAP1 (rs1057141, rs1135216) and TAP2 (rs2228396, rs241447, rs67511411, rs141555015) were determined in 173 PTB patients and 164 healthy subjects. Our findings showed that rs1135216 AG, GG and AG+GG genotypes increased the risk of PTB in comparison with AA (OR=2...
February 2016: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/26686423/network-assisted-analysis-of-primary-sj%C3%A3-gren-s-syndrome-gwas-data-in-han-chinese
#14
Kechi Fang, Kunlin Zhang, Jing Wang
Primary Sjögren's syndrome (pSS) is a complex autoimmune disorder. So far, genetic research in pSS has lagged far behind and the underlying biological mechanism is unclear. Further exploring existing genome-wide association study (GWAS) data is urgently expected to uncover disease-related gene combination patterns. Herein, we conducted a network-based analysis by integrating pSS GWAS in Han Chinese with a protein-protein interactions network to identify pSS candidate genes. After module detection and evaluation, 8 dense modules covering 40 genes were obtained for further functional annotation...
2015: Scientific Reports
https://www.readbyqxmd.com/read/26611618/frequent-hla-class-i-alterations-in-human-prostate-cancer-molecular-mechanisms-and-clinical-relevance
#15
Francisco Javier Carretero, Ana Belen Del Campo, Jose Francisco Flores-Martín, Rosa Mendez, Cesar García-Lopez, Jose Manuel Cozar, Victoria Adams, Stephen Ward, Teresa Cabrera, Francisco Ruiz-Cabello, Federico Garrido, Natalia Aptsiauri
Reduced expression of HLA class I is an important immune escape mechanism from cytotoxic T cells described in various types of malignancy. It often correlates with poor prognosis and resistance to therapy. However, current knowledge about the frequency, underlying molecular mechanisms, and prognostic value of HLA class I and II alterations in prostate cancer (PC) is limited. Immunohistochemical analysis demonstrated that 88 % of the 42 studied cryopreserved prostate tumors have at least one type of HLA alteration as compared to adjacent normal prostate epithelium or benign hyperplasia...
January 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/26610302/the-genetic-associations-of-acute-anterior-uveitis-and-their-overlap-with-the-genetics-of-ankylosing-spondylitis
#16
P C Robinson, P J Leo, J J Pointon, J Harris, K Cremin, L A Bradbury, S Stebbings, A A Harrison, D M Evans, E L Duncan, B P Wordsworth, M A Brown
Acute anterior uveitis (AAU) involves inflammation of the iris and ciliary body of the eye. It occurs both in isolation and as a complication of ankylosing spondylitis (AS). It is strongly associated with HLA-B*27, but previous studies have suggested that further genetic factors may confer additional risk. We sought to investigate this using the Illumina Exomechip microarray, to compare 1504 cases with AS and AAU, 1805 with AS but no AAU and 21 133 healthy controls. We also used a heterogeneity test to test the differences in effect size between AS with AAU and AS without AAU...
January 2016: Genes and Immunity
https://www.readbyqxmd.com/read/26587547/association-between-genetic-variants-and-diabetes-mellitus-in-iranian-populations-a-systematic-review-of-observational-studies
#17
REVIEW
Mehrnoosh Khodaeian, Samaneh Enayati, Ozra Tabatabaei-Malazy, Mahsa M Amoli
INTRODUCTION: Diabetes mellitus as the most prevalent metabolic disease is a multifactorial disease which is influenced by environmental and genetic factors. In this systematic review, we assessed the association between genetic variants and diabetes/its complications in studies with Iranian populations. METHODS: Google Scholar, PubMed, Scopus, and Persian web databases were systematically searched up to January 2014. The search terms were "gene," "polymorphism," "diabetes," and "diabetic complications"; nephropathy, retinopathy, neuropathy, foot ulcer, and CAD (coronary artery diseases); and Persian equivalents...
2015: Journal of Diabetes Research
https://www.readbyqxmd.com/read/26519531/hydrophobic-interactions-are-key-to-drive-the-association-of-tapasin-with-peptide-transporter-subunit-tap2
#18
Elke Rufer, Danny Kägebein, Ralf M Leonhardt, Michael R Knittler
The transporter associated with Ag processing (TAP) translocates proteasomally derived cytosolic peptides into the endoplasmic reticulum. TAP is a central component of the peptide-loading complex (PLC), to which tapasin (TPN) recruits MHC class I (MHC I) and accessory chaperones. The PLC functions to facilitate and optimize MHC I-mediated Ag presentation. The heterodimeric peptide transporter consists of two homologous subunits, TAP1 and TAP2, each of which contains an N-terminal domain (N-domain) in addition to a conserved transmembrane (TM) core segment...
December 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/26448050/inherited-inflammatory-response-genes-are-associated-with-b-cell-non-hodgkin-s-lymphoma-risk-and-survival
#19
Kaspar René Nielsen, Rudi Steffensen, Mette Dahl Bendtsen, Maria Rodrigo-Domingo, John Baech, Thure Mors Haunstrup, Kim Steve Bergkvist, Alexander Schmitz, Julie Stoeveve Boedker, Preben Johansen, Karen Dybkaeær, Martin Boeøgsted, Hans Erik Johnsen
BACKGROUND: Malignant B-cell clones are affected by both acquired genetic alterations and by inherited genetic variations changing the inflammatory tumour microenvironment. METHODS: We investigated 50 inflammatory response gene polymorphisms in 355 B-cell non-Hodgkin's lymphoma (B-NHL) samples encompassing 216 diffuse large B cell lymphoma (DLBCL) and 139 follicular lymphoma (FL) and 307 controls. The effect of single genes and haplotypes were investigated and gene-expression analysis was applied for selected genes...
2015: PloS One
https://www.readbyqxmd.com/read/26324772/use-of-functional-polymorphisms-to-elucidate-the-peptide-binding-site-of-tap-complexes
#20
Jie Geng, Irina D Pogozheva, Henry I Mosberg, Malini Raghavan
TAP1/TAP2 complexes translocate peptides from the cytosol to the endoplasmic reticulum lumen to enable immune surveillance by CD8(+) T cells. Peptide transport is preceded by peptide binding to a cytosol-accessible surface of TAP1/TAP2 complexes, but the location of the TAP peptide-binding pocket remains unknown. Guided by the known contributions of polymorphic TAP variants to peptide selection, we combined homology modeling of TAP with experimental measurements to identify several TAP residues that interact with peptides...
October 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
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