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MHC molecules

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https://www.readbyqxmd.com/read/28094303/genetic-polymorphisms-of-rs3077-and-rs9277535-in-hla-dp-associated-with-systemic-lupus-erythematosus-in-a-chinese-population
#1
Junlong Zhang, Wenli Zhan, Bin Yang, Anning Tian, Lin Chen, Yun Liao, Yongkang Wu, Bei Cai, Lanlan Wang
Although the SLE risk gene loci of HLA-DR and HLA-DQ within the major histocompatibility complex (MHC) region has been gradually revealed by recent Genome-Wide Association studies (GWAS), the association of HLA-DP polymorphisms with SLE was minimally reported. Considering that the variants in rs3077 and rs9277535 in the HLA-DP region could influence the immune response by affecting antigen presentation of HLA class II molecules to CD4(+) T cells, the present study aimed to explore the role of HLA-DP polymorphisms in SLE...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28094290/protein-arginine-methyltransferase-1-prmt1-represses-mhc-ii-transcription-in-macrophages-by-methylating-ciita
#2
Zhiwen Fan, Jianfei Li, Ping Li, Qing Ye, Huihui Xu, Xiaoyan Wu, Yong Xu
Efficient presentation of alien antigens triggers activation of T lymphocytes and robust host defense against invading pathogens. This pathophysiological process relies on the expression of major histocompatibility complex (MHC) molecules in antigen presenting cells such as macrophages. Aberrant MHC II transactivation plays a crucial role in the pathogenesis of atherosclerosis. Class II transactivator (CIITA) mediates MHC II induction by interferon gamma (IFN-γ). CIITA activity can be fine-tuned at the post-translational level, but the mechanisms are not fully appreciated...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28088526/subcutaneous-immunization-with-streptococcus-pneumoniae-gapdh-confers-effective-protection-in-mice-via-tlr2-and-tlr4
#3
Xiaoyu Sun, Jichao Wang, Jie Zhou, Hong Wang, Xiaofang Wang, Jingwen Wu, Yujuan He, Yibing Yin, Xuemei Zhang, Wenchun Xu
The surface localized Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of Streptococcus pneumoniae is best known as housekeeping protein. Currently, GAPDH has been recognized as moonlighting protein and virulent factor. Therefore, we investigate whether GAPDH can act as a suitable vaccine candidate protein to prevent pneumococcal infection. In this study, mice received subcutaneous vaccination with recombinant GAPDH followed by challenge with D39 and 19F showing higher survival rate and lower bacterial loads in nasal washes and lung homogenates than control...
January 12, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28078358/major-histocompatibility-complex-haplotyping-and-long-amplicon-allele-discovery-in-cynomolgus-macaques-from-chinese-breeding-facilities
#4
Julie A Karl, Michael E Graham, Roger W Wiseman, Katelyn E Heimbruch, Samantha M Gieger, Gaby G M Doxiadis, Ronald E Bontrop, David H O'Connor
Very little is currently known about the major histocompatibility complex (MHC) region of cynomolgus macaques (Macaca fascicularis; Mafa) from Chinese breeding centers. We performed comprehensive MHC class I haplotype analysis of 100 cynomolgus macaques from two different centers, with animals from different reported original geographic origins (Vietnamese, Cambodian, and Cambodian/Indonesian mixed-origin). Many of the samples were of known relation to each other (sire, dam, and progeny sets), making it possible to characterize lineage-level haplotypes in these animals...
January 11, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28077434/transfer-of-allogeneic-cd4-t-cells-rescues-cd8-t-cells-in-anti-pd-l1-resistant-tumors-leading-to-tumor-eradication
#5
Ainhoa Arina, Theodore G Karrison, Eva Galka, Karin Schreiber, Ralph R Weichselbaum, Hans Schreiber
Adoptively transferred CD8(+) T cells can stabilize the size of solid tumors over long periods of time by exclusively recognizing antigen cross-presented on tumor stroma. However, these tumors eventually escape T cell-mediated growth control. The aim of this study was to eradicate such persistent cancers. In our model, the SIYRYYGL antigen is expressed by cancer cells that lack the MHC-I molecule K(b) needed for direct presentation, but the antigen is picked up and cross-presented by tumor stroma. A single injection of antigen-specific 2C CD8(+) T cells caused long-term inhibition of tumor growth, but without further intervention, tumors started to progress after approximately 3 months...
January 11, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28063475/characterisation-of-monoclonal-antibodies-specific-for-hamster-leukocyte-differentiation-molecules
#6
Jennifer Rees, David Haig, Victoria Mack, William C Davis
Flow cytometry was used to identify mAbs that recognize conserved epitopes on hamster leukocyte differentiation molecules (hLDM) and also to characterize mAbs developed against hLDM. Initial screening of mAbs developed against LDMs in other species yielded mAbs specific for the major histocompatibility (MHC) II molecule, CD4 and CD18. Screening of sets of mAbs developed against hLDM yielded 22 new mAbs, including additional mAbs to MHC II molecules and mAbs that recognize LDMs expressed on all leukocytes, granulocytes, all lymphocytes, all T cells, a subset of T cells, or on all B cells...
January 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/28062921/targeted-deletion-of-traf2-allows-immunosuppression-free-islet-allograft-survival-in-mice
#7
Jeanette E Villanueva, Stacey N Walters, Mitsuru Saito, Elisabeth K Malle, Nathan W Zammit, Katherine A Watson, Robert Brink, Nicole L La Gruta, Stephen I Alexander, Shane T Grey
AIMS/HYPOTHESIS: Administration of anti-CD40 ligand (CD40L) antibodies has been reported to allow long-term islet allograft survival in non-human primates without the need for exogenous immunosuppression. However, the use of anti-CD40L antibodies was associated with thromboembolic complications. Targeting downstream intracellular components shared between CD40 and other TNF family co-stimulatory molecules could bypass these complications. TNF receptor associated factor 2 (TRAF2) integrates multiple TNF receptor family signalling pathways that are critical for T cell activation and may be a central node of alloimmune responses...
January 6, 2017: Diabetologia
https://www.readbyqxmd.com/read/28061947/b-lymphocytes-forming-follicle-like-structures-in-the-lung-tissue-of-tuberculosis-infected-mice-dynamics-phenotypes-and-functional-activity
#8
Irina Linge, Alexander Dyatlov, Elena Kondratieva, Vadim Avdienko, Alexander Apt, Tatiana Kondratieva
During tuberculosis (TB) infection, B cells form follicles in close vicinity of lung granuloma. We assessed the dynamics of follicle formation, surface phenotypes and functional activity of lung B cells during TB course in genetically susceptible mice. The follicles appeared early post infection and peaked at weeks 7-8. Lung B cells resembled classical B2 cells (CD19(+)IgMloIgD(hi)CD1d(-)CD21/35(int)CD5(-)CD11b(-)CD43(-)), but differed from them by the absence of B2 marker CD23. Lung B-cells constitutively expressed MHC II molecules, presented mycobacterial antigens to immune CD4(+) T-cells and produced high amounts of IL-6 and IL-11, but no classical type 1 (TNF-α, IFN-γ), or anti-inflammatory (IL-10, TGF-β) cytokines...
January 2017: Tuberculosis
https://www.readbyqxmd.com/read/28060313/generation-of-human-monocyte-derived-dendritic-cells-from-whole-blood
#9
Wilfried Posch, Cornelia Lass-Flörl, Doris Wilflingseder
Dendritic cells (DCs) recognize foreign structures of different pathogens, such as viruses, bacteria, and fungi, via a variety of pattern recognition receptors (PRRs) expressed on their cell surface and thereby activate and regulate immunity. The major function of DCs is the induction of adaptive immunity in the lymph nodes by presenting antigens via MHC I and MHC II molecules to naïve T lymphocytes. Therefore, DCs have to migrate from the periphery to the lymph nodes after the recognition of pathogens at the sites of infection...
December 24, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28057216/histone-acetylation-and-the-regulation-of-major-histocompatibility-class-ii-gene-expression
#10
K Suzuki, Y Luo
Major histocompatibility complex (MHC) class II molecules are essential for processing and presenting exogenous pathogen antigens to activate CD4(+) T cells. Given their central role in adaptive immune responses, MHC class II genes are tightly regulated in a tissue- and activation-specific manner. The regulation of MHC class II gene expression involves various transcription factors that interact with conserved proximal cis-acting regulatory promoter elements, as well as MHC class II transactivator that interacts with a variety of chromatin remodeling machineries...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28057175/pour-comprendre-l%C3%A2-activation-lymphocytaire-t
#11
Jeanne Galaine, Yann Godet, Olivier Adotévi
T cells activation is a finely regulated process to establish an effective anti-infectious or antitumor immune response while avoiding harmful autoimmune reactions. Although T cells are considered to be the main protagonists of the antitumor immune response, they act in interaction with other immune cells. The meeting of naive T cells with dendritic cells induces their differentiation into effector cells following the recognition of the peptide-MHC complex by the T cell receptor. The interaction of costimulatory molecules present on the surface of T cells with their ligand (s) expressed by mature dendritic cells contribute to the optimal T cell activation and to the formation of the immunological synapse...
November 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/28051183/hiv-1-env-associates-with-hla-c-free-chains-at-the-cell-membrane-modulating-viral-infectivity
#12
Michela Serena, Francesca Parolini, Priscilla Biswas, Francesca Sironi, Almudena Blanco Miranda, Elisa Zoratti, Maria Teresa Scupoli, Serena Ziglio, Agustin Valenzuela-Fernandez, Davide Gibellini, Maria Grazia Romanelli, Antonio Siccardi, Mauro Malnati, Alberto Beretta, Donato Zipeto
HLA-C has been demonstrated to associate with HIV-1 envelope glycoprotein (Env). Virions lacking HLA-C have reduced infectivity and increased susceptibility to neutralizing antibodies. Like all others MHC-I molecules, HLA-C requires β2-microglobulin (β2m) for appropriate folding and expression on the cell membrane but this association is weaker, thus generating HLA-C free-chains on the cell surface. In this study, we deepen the understanding of HLA-C and Env association by showing that HIV-1 specifically increases the amount of HLA-C free chains, not bound to β2m, on the membrane of infected cells...
January 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28040582/folate-deficiency-affects-dendritic-cell-function-and-subsequent-t-helper-cell-differentiation
#13
Chi-Heng Wu, Tzu-Chien Huang, Bi-Fong Lin
Insufficient folate status may be related to the increasing prevalence of immune- or inflammation-related chronic diseases. To investigate the effects of folate on immune regulation, we examined the impact of folate deficiency (FD) on dendritic cell (DC) maturation and function and, thus, T helper (Th) cells differentiation. First, bone marrow-derived DCs (BMDCs) were generated from BALB/c mice bone marrow cells cultured in folate-containing (F-BMDCs) or folate-deficient (FD-BMDCs) medium. FD-BMDC displayed more immature phenotype including reduced levels of major histocompatibility complex class II (MHC II), co-stimulatory molecules and characteristic of higher endocytic activity...
November 20, 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28032847/molecular-markers-of-systemic-autoimmune-disorders-the-expression-of-mhc-located-hsp70-genes-is-significantly-associated-with-autoimmunity-development
#14
Martina Mišunová, Tana Svitálková, Lenka Pleštilová, Olga Kryštufková, Dana Tegzová, Radka Svobodová, Marketa Hušáková, Michal Tomčík, Radim Bečvář, Jakub Závada, Herman Mann, Libor Kolesár, Antonij Slavčev, Jiri Vencovský, Peter Novota
OBJECTIVES: To analyse the expression regulation of two inducible HSP70 genes - HSPA1A and HSPA1B - located within the major histocompatibility complex (MHC) in patients with various systemic autoimmune diseases and to prove the reliability of MHC-located HSP70 genes as molecular markers reflecting the autoimmune process. METHODS: 94 adult patients with idiopathic inflammatory myopathy (IIM, n=31), systemic lupus erythematosus (SLE, n=31) or systemic sclerosis (SSc, n=32) and 37 healthy individuals were analysed...
December 28, 2016: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28027623/expression-of-a-chimeric-antigen-receptor-specific-for-donor-hla-class-i-enhances-the-potency-of-human-regulatory-t-cells-in-preventing-human-skin-transplant-rejection
#15
Dominic A Boardman, Christina Philippeos, Gilbert O Fruhwirth, Mohammad A A Ibrahim, Rosalind F Hannen, Dianne Cooper, Federica M Marelli-Berg, Fiona M Watt, Robert I Lechler, John Maher, Lesley A Smyth, Giovanna Lombardi
Regulatory T cell (Treg) therapy using recipient-derived Tregs expanded ex vivo is currently being investigated clinically by us and others as a means of reducing allograft rejection following organ transplantation. Data from animal models has demonstrated that adoptive transfer of allospecific Tregs offers greater protection from graft rejection compared to polyclonal Tregs. Chimeric antigen receptors (CAR) are clinically-translatable synthetic fusion proteins which can redirect the specificity of T cells towards designated antigens...
December 27, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/28018349/allorecognition-by-t-lymphocytes-and-allograft-rejection
#16
REVIEW
Jose Marino, Joshua Paster, Gilles Benichou
Recognition of donor antigens by recipient T cells in secondary lymphoid organs initiates the adaptive inflammatory immune response leading to the rejection of allogeneic transplants. Allospecific T cells become activated through interaction of their T cell receptors with intact allogeneic major histocompatibility complex (MHC) molecules on donor cells (direct pathway) and/or donor peptides presented by self-MHC molecules on recipient antigen-presenting cells (APCs) (indirect pathway). In addition, recent studies show that alloreactive T cells can also be stimulated through recognition of allogeneic MHC molecules displayed on recipient APCs (MHC cross-dressing) after their transfer via cell-cell contact or through extracellular vesicles (semi-direct pathway)...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28011995/delivery-of-foreign-cytotoxic-t-lymphocyte-epitopes-to-tumor-tissues-for-effective-antitumor-immunotherapy-against-pre-established-solid-tumors-in-mice
#17
Herbert W Kavunja, Shuyao Lang, Suttipun Sungsuwan, Zhaojun Yin, Xuefei Huang
Cytotoxic T lymphocyte (CTL) can have remarkable abilities to kill tumor cells. However, the establishment of successful CTL-based anticancer therapy has met with many challenges. Within tumor cells, there exist subpopulations with low or no expression of the targeted antigen (termed as antigen-loss variants). In addition, tumor cells can downregulate the levels of major histocompatibility complex class I (MHC-I) molecules on cell surface due to immune pressure. As a result, some tumor cells can escape the immune pressure bestowed by CTLs, resulting in treatment failure...
December 23, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28011936/the-mhc-class-ii-immunopeptidome-of-lymph-nodes-in-health-and-in-chemically-induced-colitis
#18
Tim Fugmann, Adriana Sofron, Danilo Ritz, Franziska Bootz, Dario Neri
We recently described a mass spectrometry-based methodology that enables the confident identification of hundreds of peptides bound to murine MHC class II (MHCII) molecules. In this article, we describe its application to the characterization of MHCII-bound peptides isolated from lymph nodes (LNs) of C57BL/6 mice. More than 1000 peptides could be identified in individual analyses, allowing a direct comparison of the MHCII peptidome in different types of normal LNs or in animals with colitis. The peptide length distribution and consensus sequences in axillary, brachial, inguinal, and mesenteric LNs were virtually identical, and a substantial portion of identified peptides corresponded to proteins found in all LNs...
December 23, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28011506/distant-bystander-effect-of-reic-dkk3-gene-therapy-through-immune-system-stimulation-in-thoracic-malignancies
#19
Ken Suzawa, Kazuhiko Shien, Huang Peng, Masakiyo Sakaguchi, Masami Watanabe, Shinsuke Hashida, Yuho Maki, Hiromasa Yamamoto, Shuta Tomida, Junichi Soh, Hiroaki Asano, Kazunori Tsukuda, Yasutomo Nasu, Hiromi Kumon, Shinichiro Miyoshi, Shinichi Toyooka
BACKGROUND: Reduced expression in immortalized cell (REIC)/Dickkoph-3 (DKK3) is a tumor-suppressor gene, and its overexpression by adenovirus vector (Ad-REIC) exhibits a remarkable therapeutic effect on various human cancer types through a mechanism triggered by endoplasmic reticulum stress. MATERIALS AND METHODS: We examined the direct anti-tumor effect of Ad-REIC gene therapy on lung cancer and malignant mesothelioma cell lines in vitro, and the distant bystander effect using immunocompetent mouse allograft models with bilateral flank tumors...
January 2017: Anticancer Research
https://www.readbyqxmd.com/read/27999739/tlr7-based-cancer-immunotherapy-decreases-intratumoral-myeloid-derived-suppressor-cells-and-blocks-their-immunosuppressive-function
#20
Thibaud Spinetti, Lorenzo Spagnuolo, Inès Mottas, Chiara Secondini, Marina Treinies, Curzio Rüegg, Christian Hotz, Carole Bourquin
Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells with the capacity to inhibit immunological responses. During cancer progression, MDSC are recruited to the tumor sites and secondary lymphoid organs, leading to the suppression of the antitumor function of NK and T cells. Here, we show that the TLR7/8 agonist resiquimod (R848) has a direct effect on MDSC populations in tumor-bearing mice. Systemic application of R848 led to a rapid reduction in both intratumoral and circulating MDSC...
2016: Oncoimmunology
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