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Mhc class i

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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
#1
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/29151581/human-pbmc-transferred-murine-mhc-class-i-ii-deficient-nog-mice-enable-long-term-evaluation-of-human-immune-responses
#2
Tomonori Yaguchi, Asuka Kobayashi, Takashi Inozume, Kenji Morii, Haruna Nagumo, Hiroshi Nishio, Takashi Iwata, Yuyo Ka, Ikumi Katano, Ryoji Ito, Mamoru Ito, Yutaka Kawakami
Immunodeficient mice engrafted with human peripheral blood cells are promising tools for in vivo analysis of human patient individual immune responses. However, when human peripheral blood mononuclear cells (PBMCs) are transferred into NOG (NOD/Shi-scid, IL-2rg(null)) mice, severe graft versus host disease (GVHD) hinders long term detailed analysis. Administration of human PBMCs into newly developed murine MHC class I- and class II-deficient NOG (NOG-dKO; NOG- Iab, B2m-double-knockout) mice showed sufficient engraftment of human immune cells with little sign of GVHD...
November 20, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29151514/a-case-of-dermatomyositis-complicated-by-digital-ischemia-and-lung-adenocarcinoma-in-a-patient-with-positive-anti-signal-recognition-particle-antibodies
#3
Takashi Nawata, Makoto Kubo, Hitomi Mitsui, Keiji Oishi, Masatoshi Omoto, Takashi Kanda, Masafumi Yano
A 58-year-old Japanese woman was diagnosed with anti-signal recognition particle (SRP)-positive dermatomyositis associated with Sjögren's syndrome, rheumatoid arthritis and lung adenocarcinoma. She presented with cutaneous lesions, including ulceration of her right middle finger. Tissue specimens obtained from her right deltoid muscle were positive for CD4(+) T-cell infiltration and the sarcolemma showed the upregulation of major histocompatibility complex (MHC) class I antigens. The present case suggests that overlapping autoimmune diseases or complications of malignancy may result in an atypical clinical presentations and histological findings in patients with anti-SRP antibody-positive dermatomyositis...
November 20, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29150238/a-t-cell-receptor-locus-harbors-a-malaria-specific-immune-response-gene
#4
Natalija Van Braeckel-Budimir, Stephanie Gras, Kristin Ladell, Tracy M Josephs, Lecia Pewe, Stina L Urban, Kelly L Miners, Carine Farenc, David A Price, Jamie Rossjohn, John T Harty
Immune response (Ir) genes, originally proposed by Baruj Benacerraf to explain differential antigen-specific responses in animal models, have become synonymous with the major histocompatibility complex (MHC). We discovered a non-MHC-linked Ir gene in a T cell receptor (TCR) locus that was required for CD8(+) T cell responses to the Plasmodium berghei GAP5040-48 epitope in mice expressing the MHC class I allele H-2D(b). GAP5040-48-specific CD8(+) T cell responses emerged from a very large pool of naive Vβ8...
November 10, 2017: Immunity
https://www.readbyqxmd.com/read/29147604/tap1-down-regulation-elicits-immune-escape-and-poor-prognosis-in-colorectal-cancer
#5
Agnes Ling, Anna Löfgren-Burström, Pär Larsson, Xingru Li, Maria L Wikberg, Åke Öberg, Roger Stenling, Sofia Edin, Richard Palmqvist
The anti-tumor immune response has been shown to be of great prognostic importance in colorectal cancer (CRC) and so has the tumors ability for immune evasion. Our aim of this study was to investigate tumor factors that influence immunity. We used a gene expression array to search for potential mechanisms of tumor immune escape. One candidate gene identified was TAP1, involved in antigen presentation by MHC class I. TAP1 protein expression was evaluated by immunohistochemistry in 436 CRC patients of the Colorectal Cancer in Umeå Study cohort...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29142130/effective-priming-of-hsv-specific-cd8-t-cells-in-vivo-does-not-require-infected-dendritic-cells
#6
Paul G Whitney, Christina Makhlouf, Beth MacLeod, Joel Z Ma, Elise Gressier, Marie Greyer, Katharina Hochheiser, Annabell Bachem, Ali Zaid, David Voehringer, William R Heath, Mayura V Wagle, Ian Parish, Tiffany A Russell, Stewart A Smith, David C Tscharke, Thomas Gebhardt, Sammy Bedoui
Resolution of virus infections depends on the priming of virus-specific CD8(+) T cells by dendritic cells (DC). While this process requires MHC class I-restricted antigen presentation by DC, the relative contribution to CD8(+) T cell priming by infected DC is less clear. We have addressed this question in the context of a peripheral infection with herpes simplex virus type 1 (HSV). Assessing the endogenous, polyclonal HSV-specific CD8(+) T cell response, we found that effective in vivo T cell priming depended on the presence of DC subsets specialized in cross-presentation while Langerhans cells and plasmacytoid DC were dispensable...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29140228/co-factor-independent-phosphoglycerate-mutase-of-leishmania-donovani-modulates-macrophage-signalling-and-promotes-t-cell-repertoires-bearing-epitopes-for-both-mhc-i-and-mhc-ii
#7
Manish K Singh, Fauzia Jamal, Amit K Dubey, Pushkar Shivam, Sarita Kumari, Pushpanjali, Ghufran Ahmed, Manas R Dikhit, S Narayan, V N R DAS, Krishna Pandey, K K Sinha, P DAS, Shubhankar K Singh
Immunoactivation depends upon the antigen potential to modulate T-cell repertoires. The present study has enumerated the effect of 61 kDa recombinant Leishmania donovani co-factor-independent phosphoglycerate mutase (rLd-iPGAM) on mononuclear cells of healthy and treated visceral leishmaniasis subjects as well as on THP-1 cell line. rLd-iPGAM stimulation induced higher expression of interleukin-1β (IL-1β) in the phagocytic cell, its receptor and CD69 on T-cell subsets. These cellular activations resulted in upregulation of host-protective cytokines IL-2, IL-12, IL-17, tumour necrosis factor-α and interferon-γ, and downregulation of IL-4, IL-10 and tumour growth factor-β...
November 15, 2017: Parasitology
https://www.readbyqxmd.com/read/29134258/novel-full-length-major-histocompatibility-complex-class-i-allele-discovery-and-haplotype-definition-in-pig-tailed-macaques
#8
Matthew R Semler, Roger W Wiseman, Julie A Karl, Michael E Graham, Samantha M Gieger, David H O'Connor
Pig-tailed macaques (Macaca nemestrina, Mane) are important models for human immunodeficiency virus (HIV) studies. Their infectability with minimally modified HIV makes them a uniquely valuable animal model to mimic human infection with HIV and progression to acquired immunodeficiency syndrome (AIDS). However, variation in the pig-tailed macaque major histocompatibility complex (MHC) and the impact of individual transcripts on the pathogenesis of HIV and other infectious diseases is understudied compared to that of rhesus and cynomolgus macaques...
November 13, 2017: Immunogenetics
https://www.readbyqxmd.com/read/29133348/non-pathogenic-colonization-with-chlamydia-in-the-gastrointestinal-tract-as-oral-vaccination-for-inducing-transmucosal-protection
#9
Luying Wang, Cuiming Zhu, Tianyuan Zhang, Qi Tian, Nu Zhang, Sandra Morrison, Richard Morrison, Min Xue, Guangming Zhong
Chlamydia has been detected in the gastrointestinal tracts of humans and animals. We now report that gastrointestinal Chlamydia muridarum is able to induce robust transmucosal protection in mice. C. muridarum colonization in the gastrointestinal tract correlated with both a shortened course of C. muridarum genital infection and stronger protection against subsequent genital tract challenge infection. Mice pre-inoculated intragastrically with C. muridarum became highly resistant to subsequent C. muridarum infection in the genital tract, resulting in prevention of pathology in the upper genital tract...
November 13, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29132960/influenza-derived-peptides-cross-react-with-allergens-and-provide-asthma-protection
#10
Chrysanthi Skevaki, Christoph Hudemann, Mikhail Matrosovich, Christian Möbs, Sinu Paul, Andreas Wachtendorf, Bilal Alashkar Alhamwe, Daniel P Potaczek, Stefanie Hagner, Diethard Gemsa, Holger Garn, Alessandro Sette, Harald Renz
BACKGROUND: The hygiene hypothesis is the leading concept to explain the current asthma epidemic, which is built on the observation that a lack of bacterial contact early in life induces allergic Th2 immune responses. OBJECTIVE: Since little is known about the contribution of respiratory viruses in this context, we evaluated the effect of prior influenza-infection on the development of allergic asthma. METHODS: Mice were infected with influenza and once recovered, subjected to an ovalbumin or house dust mite-induced experimental asthma protocol...
November 10, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29132135/increased-th1-th17-responses-contribute-to-low-grade-inflammation-in-age-related-macular-degeneration
#11
Jiajia Chen, Wenzhan Wang, Qiuming Li
BACKGROUND/AIMS: Age-related macular degeneration (AMD) is the primary cause of senior blindness in developed countries. Mechanisms underlying initiation and development of AMD remained known. METHODS: We examined the CD4+ T cell compartments and their functions in AMD patients. RESULTS: AMD patients presented significantly higher frequencies of interferon (IFN)-γ-expressing and interleukin (IL)-17-expressing CD4+ T cells than healthy controls...
November 13, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29131441/genetic-and-epigenetic-regulation-of-major-histocompatibility-complex-class-i-gene-expression-in-bovine-trophoblast-cells
#12
Bi Shi, Aaron J Thomas, Abby D Benninghoff, Benjamin R Sessions, Qinggang Meng, Parveen Parasar, Heloisa M Rutigliano, Kenneth L White, Christopher J Davies
PROBLEM: The regulatory mechanisms governing differential expression of classical major histocompatibility complex (MHC) class I (MHC-Ia) and non-classical MHC class I (MHC-Ib) genes are poorly understood. METHOD OF STUDY: Quantitative reverse transcription- polymerase chain reaction (PCR) was used to compare the abundance of MHC-I transcripts and related transcription factors in peripheral blood mononuclear cells (PBMC) and placental trophoblast cells (PTC). Methylation of MHC-I CpG islands was detected by bisulfite treatment and next-generation sequencing...
November 12, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/29129453/hepatitis-b-virus-core-particles-containing-multiple-epitopes-confer-protection-against-enterovirus-71-and-coxsackievirus-a16-infection-in-mice
#13
Chunling Huo, Jie Yang, Lei Lei, Lei Qiao, Jiantao Xin, Zishu Pan
Human enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the two major causative agents of hand-foot-and-mouth disease (HFMD). To investigate novel combined vaccines to prevent EV71 and CA16 infection, we constructed chimeric virus-like particles (tHBc/SPA or tHBc/SP VLPs) displaying conserved epitopes of EV71 (aa 208-222 of VP1 and aa 248-263 of VP2) and CA16 (aa271-285 of VP1) using a truncated hepatitis B virus core carrier (tHBc). Immunization with the chimeric VLPs induced epitope- or virus-specific IgG and neutralization antibodies against EV71 and CA16 in the mice...
November 9, 2017: Vaccine
https://www.readbyqxmd.com/read/29126597/role-of-autophagy-in-mhc-class-i-restricted-antigen-presentation
#14
Luc Van Kaer, Vrajesh V Parekh, J Luke Postoak, Lan Wu
Major histocompatibility complex (MHC) class I molecules present peptide antigens to MHC class I-restricted CD8(+) T lymphocytes. The peptides loaded onto MHC class I molecules are typically derived from cytosolic antigens, which includes both self and foreign proteins. In addition to this classical MHC class I antigen presentation pathway, some cell types, especially dendritic cells can present antigens from exogenous sources to MHC class I-restricted CD8(+) T cells, in a process called cross-presentation...
November 8, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29123465/autoimmunity-as-a-driving-force-of-cognitive-evolution
#15
Serge Nataf
In the last decades, increasingly robust experimental approaches have formally demonstrated that autoimmunity is a physiological process involved in a large range of functions including cognition. On this basis, the recently enunciated "brain superautoantigens" theory proposes that autoimmunity has been a driving force of cognitive evolution. It is notably suggested that the immune and nervous systems have somehow co-evolved and exerted a mutual selection pressure benefiting to both systems. In this two-way process, the evolutionary-determined emergence of neurons expressing specific immunogenic antigens (brain superautoantigens) has exerted a selection pressure on immune genes shaping the T-cell repertoire...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29115832/improved-prediction-of-bovine-leucocyte-antigens-bola-presented-ligands-by-use-of-mass-spectrometry-determined-ligand-and-in-vitro-binding-data
#16
Morten Nielsen, Tim Connelley, Nicola Ternette
Peptide binding to MHC class I molecules is the single most selective step in antigen presentation and the strongest single correlate to peptide cellular immunogenicity. The cost of experimentally characterizing the rules of peptide presentation for a given MHC-I molecule is extensive, and predictors of peptide-MHC interactions constitute an attractive alternative. Recently, an increasing amount of MHC presented peptides identified by mass spectrometry (MS ligands) has been published. Handling and interpretation of MS ligand data is, in general, challenging due to the polyspecificity nature of the data...
November 14, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/29113227/low-dose-valproic-acid-with-low-dose-gemcitabine-augments-mhc-class-i-related-chain-a-b-expression-without-inducing-the-release-of-soluble-mhc-class-i-related-chain-a-b
#17
Tomoharu Miyashita, Kenji Miki, Takashi Kamigaki, Isamu Makino, Hidehiro Tajima, Shinichi Nakanuma, Hironori Hayashi, Hiroyuki Takamura, Sachio Fushida, Ali K Ahmed, John W Harmon, Tetsuo Ohta
To improve natural killer group 2 member D (NKG2D)-dependent cytotoxicity, the inhibition of cleavage and release of major histocompatibility complex class 1-related chain (MIC) molecules from the tumor surface are required. Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, is able to induce cell-surface MICA/B on tumor cells. In the present study, the ability of VPA and gemcitabine (GEM) to upregulate MICA/B in pancreatic cancer cells was investigated, resulting in the inhibition of cleavage and release of MIC molecules from the tumor surface...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29112686/interferon-regulatory-factor-1-priming-of-tumour-derived-exosomes-enhances-the-antitumour-immune-response
#18
Mu-Qing Yang, Qiang Du, Patrick R Varley, Julie Goswami, Zhihai Liang, Ronghua Wang, Hui Li, Donna B Stolz, David A Geller
BACKGROUND: Tumour-derived exosomes (TEXs) have a potential for application in cancer vaccines. Whether TEXs after induction by interferon regulatory factor 1 (IRF-1) are capable of enhancing the antitumour response remains to be determined. METHODS: Exosomes released by tumour cells infected with IRF-1-expressing adenovirus (IRF-1-Exo) or treated with interferon-γ (IFN-Exo) were isolated via ultracentrifugation. The IRF-1 target proteins IL-15Rα and MHC class I (MHC-I) were analysed by western blot...
November 7, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29109146/peptide-splicing-by-the-proteasome
#19
Nathalie Vigneron, Violette Ferrari, Vincent Stroobant, Joanna Abi Habib, Benoit Van den Eynde
The proteasome is the major protease responsible for the production of antigenic peptides recognized by CD8+ cytolytic T cells (CTL). These peptides, generally 8-to-10 amino acid-long, are presented at the cell surface by major histocompatibility complex (MHC) class I molecules. Although for years, these peptides were believed to solely derive from linear fragments of proteins, this concept was challenged several years ago by the isolation of anti-tumor CTL that recognized spliced peptides, i.e. peptides composed of fragments originally distant in the parental protein...
November 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29107940/structure-of-the-human-mhc-i-peptide-loading-complex
#20
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
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