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https://www.readbyqxmd.com/read/28813660/neutralizing-antibody-responses-to-viral-infections-are-linked-to-the-non-classical-mhc-class-ii-gene-h2-ob
#1
Lisa K Denzin, Aly A Khan, Francesca Virdis, Jessica Wilks, Melissa Kane, Helen A Beilinson, Stanislav Dikiy, Laure K Case, Derry Roopenian, Michele Witkowski, Alexander V Chervonsky, Tatyana V Golovkina
Select humans and animals control persistent viral infections via adaptive immune responses that include production of neutralizing antibodies. The precise genetic basis for the control remains enigmatic. Here, we report positional cloning of the gene responsible for production of retrovirus-neutralizing antibodies in mice of the I/LnJ strain. It encodes the beta subunit of the non-classical major histocompatibility complex class II (MHC-II)-like molecule H2-O, a negative regulator of antigen presentation. The recessive and functionally null I/LnJ H2-Ob allele supported the production of virus-neutralizing antibodies independently of the classical MHC haplotype...
August 15, 2017: Immunity
https://www.readbyqxmd.com/read/28813459/%C3%AE-2-microglobulin-gene-duplication-in-cetartiodactyla-remains-intact-only-in-pigs-and-possibly-confers-selective-advantage-to-the-species
#2
Thong Minh Le, Quy Van Chanh Le, Dung Minh Truong, Hye-Jeong Lee, Min-Kyeung Choi, Hyesun Cho, Hak-Jae Chung, Jin-Hoi Kim, Jeong-Tae Do, Hyuk Song, Chankyu Park
Several β2-microglobulin (B2M) -bound protein complexes undertake key roles in various immune system pathways, including the neonatal Fc receptor (FcRn), cluster of differentiation 1 (CD1) protein, non-classical major histocompatibility complex (MHC), and well-known MHC class I molecules. Therefore, the duplication of B2M may lead to an increase in the biological competence of organisms to the environment. Based on the pig genome assembly SSC10.2, a segmental duplication of ~45.5 kb, encoding the entire B2M protein, was identified in pig chromosome 1...
2017: PloS One
https://www.readbyqxmd.com/read/28813417/cmtm6-maintains-the-expression-of-pd-l1-and-regulates-anti-tumour-immunity
#3
Marian L Burr, Christina E Sparbier, Yih-Chih Chan, James C Williamson, Katherine Woods, Paul A Beavis, Enid Y N Lam, Melissa A Henderson, Charles C Bell, Sabine Stolzenburg, Omer Gilan, Stuart Bloor, Tahereh Noori, David W Morgens, Michael C Bassik, Paul J Neeson, Andreas Behren, Phillip K Darcy, Sarah-Jane Dawson, Ilia Voskoboinik, Joseph A Trapani, Jonathan Cebon, Paul J Lehner, Mark A Dawson
Cancer cells exploit the expression of the programmed death-1 (PD-1) ligand 1 (PD-L1) to subvert T-cell-mediated immunosurveillance. The success of therapies that disrupt PD-L1-mediated tumour tolerance has highlighted the need to understand the molecular regulation of PD-L1 expression. Here we identify the uncharacterized protein CMTM6 as a critical regulator of PD-L1 in a broad range of cancer cells, by using a genome-wide CRISPR-Cas9 screen. CMTM6 is a ubiquitously expressed protein that binds PD-L1 and maintains its cell surface expression...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28812992/endolysosomal-degradation-of-allergenic-ole-e-1-like-proteins-analysis-of-proteolytic-cleavage-sites-revealing-t-cell-epitope-containing-peptides
#4
Sabrina Wildner, Brigitta Elsässer, Teresa Stemeseder, Peter Briza, Wai Tuck Soh, Mayte Villalba, Jonas Lidholm, Hans Brandstetter, Gabriele Gadermaier
Knowledge of the susceptibility of proteins to endolysosomal proteases provides valuable information on immunogenicity. Though Ole e 1-like proteins are considered relevant allergens, little is known about their immunogenic properties and T cell epitopes. Thus, six representative molecules, i.e., Ole e 1, Fra e 1, Sal k 5, Che a 1, Phl p 11 and Pla l 1, were investigated. Endolysosomal degradation and peptide generation were simulated using microsomal fractions of JAWS II dendritic cells. Kinetics and peptide patterns were evaluated by gel electrophoresis and mass spectrometry...
August 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28809608/treatment-of-patients-with-metastatic-cancer-using-a-major-histocompatibility-complex-class-ii-restricted-t-cell-receptor-targeting-the-cancer-germline-antigen-mage-a3
#5
Yong-Chen Lu, Linda L Parker, Tangying Lu, Zhili Zheng, Mary Ann Toomey, Donald E White, Xin Yao, Yong F Li, Paul F Robbins, Steven A Feldman, Pierre van der Bruggen, Christopher A Klebanoff, Stephanie L Goff, Richard M Sherry, Udai S Kammula, James C Yang, Steven A Rosenberg
Purpose Adoptive transfer of genetically modified T cells is being explored as a treatment for patients with metastatic cancer. Most current strategies use genes that encode major histocompatibility complex (MHC) class I-restricted T-cell receptors (TCRs) or chimeric antigen receptors to genetically modify CD8(+) T cells or bulk T cells for treatment. Here, we evaluated the safety and efficacy of an adoptive CD4(+) T-cell therapy using an MHC class II-restricted, HLA-DPB1*0401-restricted TCR that recognized the cancer germline antigen, MAGE-A3 (melanoma-associated antigen-A3)...
August 15, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28807929/human-mucosal-associated-invariant-t-mait-cells-possess-capacity-for-b-cell-help
#6
Michael S Bennett, Shubhanshi Trivedi, Anita S Iyer, J Scott Hale, Daniel T Leung
Mucosal-associated invariant T (MAIT) cells are an innate-like T-cell subset, restricted by the nonclassic MHC class I-related protein MR1 and enriched at mucosal sites. Human studies have shown an association between MAIT cells and pathogen-specific antibody responses. In this study, we investigate the effect of human MAIT cells on B cells ex vivo. We found that supernatants from microbe- or cytokine-stimulated MAIT cells, when added to purified autologous B cells, increase frequencies of plasmablasts and promote IgA, IgG, and IgM production...
August 14, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28801669/balance-between-estrogens-and-proinflammatory-cytokines-regulates-chemokine-production-involved-in-thymic-germinal-center-formation
#7
Nadine Dragin, Patrice Nancy, José Villegas, Régine Roussin, Rozen Le Panse, Sonia Berrih-Aknin
The early-onset form of Myasthenia Gravis (MG) is prevalent in women and associates with ectopic germinal centers (GCs) development and inflammation in the thymus. we aimed to investigate the contribution of estrogens in the molecular processes involved in thymic GCs formation. We examined expression of genes involved in anti-acetylcholine receptor (AChR) response in MG, MHC class II and α-AChR subunit as well as chemokines involved in GC development (CXCL13, CCL21and CXCL12). In resting conditions, estrogens have strong regulatory effects on thymic epithelial cells (TECs), inducing a decreased protein expression of the above molecules...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28791392/the-mechanism-of-de-novo-expression-of-programmed-cell-death-ligand-1-in-squamous-cell-carcinoma-of-the-lung
#8
Tomoyuki Igarashi, Koji Teramoto, Mitsuaki Ishida, Jun Hanaoka, Yataro Daigo
Immune checkpoint mechanisms such as the programmed cell death-ligand 1-programmed cell death 1 (PD‑L1-PD‑1) axis are utilized by tumor cells to evade the cytotoxicity of effector immune cells. However, environmental factors responsible for the expression of PD‑L1 on tumor cells remain to be fully elucidated. We hypothesized that an immunological interaction with tumor-infiltrating CD8+ lymphocytes (CD8+ TILs) would contribute to PD‑L1 expression in tumor cells. To verify this hypothesis, we examined the effect of interferon-γ (IFN-γ), a cytokine secreted by CD8+ TILs, on PD‑L1 expression in pulmonary squamous cell carcinomas in vitro...
August 3, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28789525/direct-loading-of-itep-delivered-ctl-epitopes-onto-mhc-class-i-complexes-on-the-dendritic-cell-surface
#9
Shuyun Dong, Peng Wang, Peng Zhao, Mingnan Chen
Cytotoxic T lymphocyte (CTL)-mediated immune responses are the primary defense mechanism against cancer and infection. CTL epitope peptides have been used as vaccines to boost CTL responses; however, the efficacy of these peptides is suboptimal. Under current vaccine formulation and delivery strategies, these vaccines are delivered into and processed inside antigen presenting cells such as dendritic cells (DCs). However, the intracellular process is not efficient, which at least partially contributes to the suboptimal efficacy of the vaccines...
August 8, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28783658/human-thymoproteasome-variations-influence-cd8-t-cell-selection
#10
Takeshi Nitta, Yuta Kochi, Ryunosuke Muro, Yoshihiko Tomofuji, Tadashi Okamura, Shigeo Murata, Harumi Suzuki, Takayuki Sumida, Kazuhiko Yamamoto, Hiroshi Takayanagi
The proteasome is a multi-subunit protease complex essential for housekeeping protein degradation and the production of the major histocompatibility complex (MHC) class I-bound antigen peptides that are essential for recognition by CD8 T cells. MHC variations dramatically contribute to T cell selection and autoimmunity, but genetic variations of peptide processing machinery including proteasome genes have been poorly explored in this context. In the computational analysis of human proteasome gene variation, we documented that PSMB11 was highly enriched for nucleotide changes that interfere with protein function...
June 2, 2017: Science Immunology
https://www.readbyqxmd.com/read/28772259/high-frequency-of-human-leukocyte-antigen-b-57-01-allele-carriers-among-hiv-infected-patients-in-serbia
#11
Marina Siljic, Dubravka Salemovic, Valentina Cirkovic, Ivana Pesic-Pavlovic, Marija Todorovic, Jovan Ranin, Gordana Dragovic, Djordje Jevtovic, Maja Stanojevic
Abacavir is an effective antiretroviral drug and one of the most commonly used nucleoside reverse transcriptase inhibitors in Serbia. А percentage of the treated patients experience a potentially life-threatening hypersensitivity reaction, which was shown to be associated with the presence of the class I MHC allele, HLA-B*57:01; hence genotyping for HLA-B*57:01 prior to starting abacavir is nowadays recommended in international HIV treatment guidelines. In Serbia, this testing became available in 2013. This study was designed to estimate the prevalence of the HLA-B*57:01 allele in Serbian HIV-1-infected patients...
August 4, 2017: Intervirology
https://www.readbyqxmd.com/read/28771693/herpes-simplex-virus-1-interferes-with-autophagy-of-murine-dendritic-cells-and-impairs-their-ability-to-stimulate-cd8-t-lymphocytes
#12
Ramachandramouli Budida, Metodi V Stankov, Katinka Döhner, Anna Buch, Diana Panayotova-Dimitrova, Kim A Tappe, Anja Pohlmann, Beate Sodeik, Georg M N Behrens
The MHC class I presentation is responsible for the presentation of viral proteins to CD8(+) T lymphocytes and mainly depends on the classical antigen processing pathway. Recently, a second pathway involving autophagy has been implicated in this process. Here, we show an increase in the capacity of murine dendritic cells to present viral antigens on MHC class I after infection with a mutant herpes simplex virus 1 (HSV-1-Δ34.5), lacking ICP34.5, when compared to its parental HSV-1 strain. The ICP34.5 protein counteracts host cell translational arrest and suppresses macroautophagy, and the lack of this protein resulted in a low viral protein abundance, which was processed and presented in an efficient way...
August 3, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28768725/immune-protection-by-a-cytomegalovirus-vaccine-vector-expressing-a-single-low-avidity-epitope
#13
Lisa Borkner, Katarzyna M Sitnik, Iryna Dekhtiarenko, Ann-Kathrin Pulm, Ronny Tao, Ingo Drexler, Luka Cicin-Sain
Experimental CMV-based vaccine vectors expressing a single MHC class I-restricted high-avidity epitope provided strong, T cell-dependent protection against viruses or tumors. In this study we tested the low-avidity epitope KCSRNRQYL, and show that a mouse CMV (MCMV) vector provides complete immune control of recombinant vaccinia virus expressing the same epitope if KCSRNRQYL is expressed within the immediate-early MCMV gene ie2 The same epitope expressed within the early M45 gene provided no protection, although MCMV vectors expressing the high-avidity epitope SSIEFARL induced protective immunity irrespective of gene expression context...
August 2, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28768206/multi-level-strategy-for-identifying-proteasome-catalyzed-spliced-epitopes-targeted-by-cd8-t-cells-during-bacterial-infection
#14
Anouk C M Platteel, Juliane Liepe, Kathrin Textoris-Taube, Christin Keller, Petra Henklein, Hanna H Schalkwijk, Rebeca Cardoso, Peter M Kloetzel, Michele Mishto, Alice J A M Sijts
Proteasome-catalyzed peptide splicing (PCPS) generates peptides that are presented by MHC class I molecules, but because their identification is challenging, the immunological relevance of spliced peptides remains unclear. Here, we developed a reverse immunology-based multi-level approach to identify proteasome-generated spliced epitopes. Applying this strategy to a murine Listeria monocytogenes infection model, we identified two spliced epitopes within the secreted bacterial phospholipase PlcB that primed antigen-specific CD8(+) T cells in L...
August 1, 2017: Cell Reports
https://www.readbyqxmd.com/read/28767728/crystal-structure-of-qa-1a-with-bound-qa-1-determinant-modifier-peptide
#15
Ge Ying, Jing Wang, Vipin Kumar, Dirk M Zajonc
Qa-1 is a non-classical Major Histocompatibility (MHC) class I molecule that generally presents hydrophobic peptides including Qdm derived from the leader sequence of classical MHC I molecules for immune surveillance by NK cells. Qa-1 bound peptides derived from the TCR Vβ8.2 of activated T cells also activates CD8+ regulatory T cells to control autoimmunity and maintain self-tolerance. Four allotypes of Qa-1 (Qa-1a-d) are expressed that are highly conserved in sequence but have several variations that could affect peptide binding to Qa-1 or TCR recognition...
2017: PloS One
https://www.readbyqxmd.com/read/28765875/quantum-dot-pmhc-multimers-vs-phycoerythrin-pmhc-tetramers-for-identification-of-hla-a-0201-restricted-phbv-core-antigen18-27-specific-t-cells
#16
Jianmeng Zhu, Yong Huang, Jing Su, Jian He, Yating Yu, Yongxiang Zhao, Xiaoling Lu
Detection of human leukocyte antigens-A2-restricted p-hepatitis B virus (HBV) core antigen‑specific cytotoxic T lymphocytes (CTLs) is important in the study of HBV immunopathogenesis and vaccine design. Currently, major histocompatibility complex (MHC) class I/peptide‑(p) MHCI tetramers are considered the optimal tools to detect antigen‑specific CTLs. However, the MHC‑tetramer technique also has certain drawbacks and is under continuous development. The quantum dot (QD) bioconjugates nanotechnology with its unique inorganic‑biological properties has been developing fast...
August 1, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28762208/two-novel-poxviruses-with-unusual-genome-rearrangements-ny_014-and-murmansk
#17
Chad Smithson, Hermann Meyer, Crystal M Gigante, Jinxin Gao, Hui Zhao, Dhwani Batra, Inger Damon, Chris Upton, Yu Li
The genome sequence and annotation of two novel poxviruses, NY_014 and Murmansk, are presented. Despite being isolated on different continents and from different hosts, the viruses are relatively similar, albeit distinct species. The closest known relative of the novel viruses is Yoka poxvirus. Five novel genes were found in these genomes, two of which were MHC class I homologs. Although the core of these genomes was well conserved, the terminal regions showed significant variability with large deletions and surprising evidence of recombination with orthopoxviruses...
July 31, 2017: Virus Genes
https://www.readbyqxmd.com/read/28761446/characteristics-of-human-endometrium-derived-mesenchymal-stem-cells-and-their-tropism-to-endometriosis
#18
Yan Cheng, Liru Li, Dejun Wang, Qiuyan Guo, Yanan He, Tian Liang, Liyuan Sun, Xiaojun Wang, Yulei Cheng, Guangmei Zhang
Human endometrial tissue has become an attractive source of mesenchymal stem cells (MSCs) for cell-based therapies because these MSCs can be easily harvested and have tumour tropism as well as reduced immunogenic and inflammatory properties. Our study aimed to obtain and characterise human endometrial mesenchymal stem cells (EMSCs) and assess their endometriosis tropism. EMSCs were successfully isolated from the endometrium of women undergoing laparoscopy for idiopathic infertility. The EMSCs presented a fibroblast-like morphology during culture...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28759104/the-interplay-between-hla-b27-and-erap1-erap2-aminopeptidases-from-antiviral-protection-to-spondyloarthritis
#19
REVIEW
Carolina Vitulano, Valentina Tedeschi, Fabiana Paladini, Rosa Sorrentino, Maria Teresa Fiorillo
The human leukocyte antigen class I gene HLA-B27 is the strongest risk factor for Ankylosing Spondylitis (AS), a chronic inflammatory arthritic disorder. More recently, the Endoplasmic Reticulum Aminopeptidases (ERAP) 1 and 2 genes have been identified by genome-wide association studies (GWAS) as additional susceptibility factors. In the ER, these aminopeptidases trim the peptides to a length suitable to fit into the groove of the MHC class I molecules. Noteworthy, an epistatic interaction between HLA-B27 and ERAP1, but not between HLA-B27 and ERAP2, has been highlighted...
July 31, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28756915/in-silico-identification-and-characterization-of-common-epitope-based-peptide-vaccine-for-nipah-and-hendra-viruses
#20
Chayan Kumar Saha, Md Mahbub Hasan, Md Saddam Hossain, Md Asraful Jahan, Abul Kalam Azad
OBJECTIVE: To explore a common B- and T-cell epitope-based vaccine that can elicit an immune response against encephalitis causing genus Henipaviruses, Hendra virus (HeV) and Nipah virus (NiV). METHODS: Membrane proteins F, G and M of HeV and NiV were retrieved from the protein database and subjected to different bioinformatics tools to predict antigenic B-cell epitopes. Best B-cell epitopes were then analyzed to predict their T-cell antigenic potentiality. Antigenic B- and T-cell epitopes that shared maximum identity with HeV and NiV were selected...
June 2017: Asian Pacific Journal of Tropical Medicine
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