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Mhc class i

Gen Murakami, Mitsuhiro Edamura, Tomonori Furukawa, Hideya Kawasaki, Isao Kosugi, Atsuo Fukuda, Toshihide Iwashita, Daiichiro Nakahara
Major histocompatibility complex class I (MHCI) is an important immune protein that is expressed in various brain regions, with its deficiency leading to extensive synaptic transmission that results in learning and memory deficits. Although MHCI is highly expressed in dopaminergic neurons, its role in these neurons has not been examined. We show that MHCI expressed in dopaminergic neurons plays a key role in suppressing reward-seeking behavior. In wild-type mice, cocaine self-administration caused persistent reduction of MHCI specifically in dopaminergic neurons, which was accompanied by enhanced glutamatergic synaptic transmission and relapse to cocaine seeking...
March 2018: Science Advances
Daniela Dukovska, Daniel Fernández-Soto, Mar Valés-Gómez, Hugh T Reyburn
The biology and function of NKG2H receptor, unlike the better characterized members of the NKG2 family NKG2A, NKG2C, and NKG2D, remains largely unclear. Here, we show that NKG2H is able to associate with the signaling adapter molecules DAP12 and DAP10 suggesting that this receptor can signal for cell activation. Using a recently described NKG2H-specific monoclonal antibody (mAb), we have characterized the expression and function of lymphocytes that express this receptor. NKG2H is expressed at the cell surface of a small percentage of peripheral blood mononuclear cell (PBMC) and is found more frequently on T cells, rather than NK cells...
2018: Frontiers in Immunology
Tirtsah Toledano, Alon Vitenshtein, Noam Stern-Ginossar, Einat Seidel, Ofer Mandelboim
Recognition of the human stress-induced ligand MHC class I polypeptide-related sequence A (MICA) by the receptor NKG2D expressed on NK cells leads to NK cell-mediated killing of the target cells. Hence, the expression of MICA must be tightly regulated, and its cell surface expression needs to be quickly downregulated to avoid inappropriate activation of immune cells. In this article, we describe a transcript variant of human MICA that has not yet been studied, which contains a 3' untranslated region of 119 nt instead of 174...
March 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Liam V Brown, Eamonn A Gaffney, Jonathan Wagg, Mark C Coles
Tumour immunotherapy is dependent upon activation and expansion of tumour-targetting immune cells, known as cytotoxic T-lymphocytes (CTLs). Cancer vaccines developed in the past have had limited success and the mechanisms resulting in failure are not well characterized. To elucidate these mechanisms, we developed a human-parametrized, in silico , agent-based model of vaccination-driven CTL activation within a clinical short-peptide vaccination context. The simulations predict a sharp transition in the probability of CTL activation, which occurs with variation in the separation rate (or off-rate) of tumour-specific immune response-inducing peptides (cognate antigen) from the major histocompatibility class I (MHC-I) receptors of dendritic cells (DCs) originally at the vaccination site...
March 2018: Journal of the Royal Society, Interface
Dinler A Antunes, Didier Devaurs, Mark Moll, Gregory Lizée, Lydia E Kavraki
The class I major histocompatibility complex (MHC) is capable of binding peptides derived from intracellular proteins and displaying them at the cell surface. The recognition of these peptide-MHC (pMHC) complexes by T-cells is the cornerstone of cellular immunity, enabling the elimination of infected or tumoral cells. T-cell-based immunotherapies against cancer, which leverage this mechanism, can greatly benefit from structural analyses of pMHC complexes. Several attempts have been made to use molecular docking for such analyses, but pMHC structure remains too challenging for even state-of-the-art docking tools...
March 12, 2018: Scientific Reports
Florian Erhard, Anne Halenius, Cosima Zimmermann, Anne L'Hernault, Daniel J Kowalewski, Michael P Weekes, Stefan Stevanovic, Ralf Zimmer, Lars Dölken
Ribosome profiling has been used to predict thousands of short open reading frames (sORFs) in eukaryotic cells, but it suffers from substantial levels of noise. PRICE ( is a computational method that models experimental noise to enable researchers to accurately resolve overlapping sORFs and noncanonical translation initiation. We experimentally validated translation using major histocompatibility complex class I (MHC I) peptidomics and observed that sORF-derived peptides efficiently enter the MHC I presentation pathway and thus constitute a substantial fraction of the antigen repertoire...
March 12, 2018: Nature Methods
Tong Wang, Fumou Sun, Yang Wang, Jiahao Jiang, Mingzhu Pan, Minne Yuan, Hang Zhang, Xiaodian Du, Kamal Hezam, Kai Song, Min Wang, Juan Zhang
Colorectal carcinoma (CRC) is one of the most common malignant cancers worldwide. The poor response of CRC to chemotherapy has whipped up the interest in targeted therapy with monoclonal antibodies for its potential efficiency. However, cetuximab, as one of the first-line targeted drugs in the treatment of CRC, has drug resistance and poor prognosis in clinic. To address this, a novel bispecific protein with CRC targeting and natural killer (NK) cell triggering was used for treatment. NK cell-mediated immunosurveillance is normally activated by the activating receptor natural killer cell receptor NK group 2, member D (NKG2D), which binds its key ligand major histocompatibility complex (MHC) class I-related chain A (MICA) expressed on the tumor cells...
April 2018: Journal of Immunotherapy
Kang Yu, Chelsea L Davidson, Agnieszka Wójtowicz, Luiz Lisboa, Ting Wang, Adriana M Airo, Jean Villard, Jeremie Buratto, Tatyana Sandalova, Adnane Achour, Atul Humar, Katia Boggian, Alexia Cusini, Christian van Delden, Adrian Egli, Oriol Manuel, Nicolas Mueller, Pierre-Yves Bochud, Deborah N Burshtyn
UL18 is a human CMV (HCMV) MHC class I (MHCI) homolog that efficiently inhibits leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1)+ NK cells. We found an association of LILRB1 polymorphisms in the regulatory regions and ligand-binding domains with control of HCMV in transplant patients. Naturally occurring LILRB1 variants expressed in model NK cells showed functional differences with UL18 and classical MHCI, but not with HLA-G. The altered functional recognition was recapitulated in binding assays with the binding domains of LILRB1...
March 12, 2018: Journal of Clinical Investigation
B Güney Saruhan, H Sağsöz, E Akbalık, M A Ketani, S Erdoğan
The mammalian testis possesses a special immunological environment because of its properties of remarkable immune privilege and effective local innate immunity. The testicular immune privilege protects immunogenic germ cells from systemic immune attack, and local innate immunity is important in preventing testicular microbial infections. Thus, this study aimed to immunohistochemically demonstrate the distribution and localization of CD68-, CD8-, MHCI- and MHCII-positive immune cells in the testes and epididymes...
March 12, 2018: Anatomia, Histologia, Embryologia
Tracey Russell, Simeon Lisovski, Mats Olsson, Gregory Brown, Rebecca Spindler, Amanda Lane, Tamara Keeley, Chris Hibbard, Carolyn J Hogg, Frédéric Thomas, Katherine Belov, Beata Ujvari, Thomas Madsen
Devil Facial Tumour Disease (DFTD), a highly contagious cancer, has decimated Tasmanian devil (Sarcophilus harrisii) numbers in the wild. To ensure its long-term survival, a captive breeding program was implemented but has not been as successful as envisaged at its launch in 2005. We therefore investigated the reproductive success of 65 captive devil pair combinations, of which 35 produced offspring (successful pairs) whereas the remaining 30 pairs, despite being observed mating, produced no offspring (unsuccessful pairs)...
March 8, 2018: Scientific Reports
Giulia Franzoni, Simon P Graham, Giovanna Sanna, Pierpaolo Angioi, Mariangela S Fiori, Antonio Anfossi, Massimo Amadori, Silvia Dei Giudici, Annalisa Oggiano
African swine fever (ASF) is a devastating disease for which there is no vaccine. The ASF virus (ASFV) can infect dendritic cell (DC), but despite the critical role these cells play in induction of adaptive immunity, few studies investigated their response to ASFV infection. We characterized the in vitro interactions of porcine monocyte-derived DCs (moDC) with a virulent (22653/14), a low virulent (NH/P68) and an avirulent (BA71V) ASFV strain. At a high multiplicity of infection (MOI = 1), all three strains infected immature moDC...
March 2018: Veterinary Microbiology
Ruth Pye, Amanda Patchett, Elspeth McLennan, Russell Thomson, Scott Carver, Samantha Fox, David Pemberton, Alexandre Kreiss, Adriana Baz Morelli, Anabel Silva, Martin J Pearse, Lynn M Corcoran, Katherine Belov, Carolyn J Hogg, Gregory M Woods, A Bruce Lyons
Devil facial tumor disease (DFTD) is renowned for its successful evasion of the host immune system. Down regulation of the major histocompatabilty complex class I molecule (MHC-I) on the DFTD cells is a primary mechanism of immune escape. Immunization trials on captive Tasmanian devils have previously demonstrated that an immune response against DFTD can be induced, and that immune-mediated tumor regression can occur. However, these trials were limited by their small sample sizes. Here, we describe the results of two DFTD immunization trials on cohorts of devils prior to their wild release as part of the Tasmanian Government's Wild Devil Recovery project...
2018: Frontiers in Immunology
Miseon Lee, In Hye Song, Sun-Hee Heo, Young-Ae Kim, In Ah Park, Won Seon Bang, Hye Seon Park, Gyungyub Gong, Hee Jin Lee
Purpose: In the presence of interferon, proteasome subunits are replaced by their inducible counterparts to form an immunoproteasome (IP) plays a key role in generation of antigenic peptides presented by MHC class I molecules, leading to elicitation of a T cell‒mediated immune response. Although the roles of IP in other cancers, and inflammatory diseases have been extensively studied, its significance in breast cancer is unclear. Materials and Methods: We investigated the expression of LMP7, an IP subunit, and its relationship with immune system components in two breast cancer cohorts...
February 26, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
Fengqiang Cao, Mengmeng Yan, Yijia Liu, Lanxia Liu, Guilei Ma
Cancer vaccines aim to induce a strong major histocompatibility complex class I (MHC-I)-restricted CD8+ cytotoxic T-cell response, which is an important prerequisite for successful cancer immunotherapy. Herein, a hyaluronic acid (HA) and antigen (ovalbumin, OVA)-decorated gold nanoparticle (AuNPs)-based (HA-OVA-AuNPs) vaccine is developed for photothermally controlled cytosolic antigen delivery using near-infrared (NIR) irradiation and is found to induce antigen-specific CD8+ T-cell responses. Chemical binding of thiolated HA and OVA to AuNPs facilitates antigen uptake of dendritic cells via receptor-mediated endocytosis...
March 6, 2018: Advanced Healthcare Materials
Joel Lanoix, Chantal Durette, Mathieu Courcelles, Émilie Cossette, Simon Comtois-Marotte, Marie-Pierre Hardy, Caroline Côté, Claude Perreault, Pierre Thibault
Significant technological advances in both affinity chromatography and mass spectrometry have facilitated the identification of peptides associated with the major histocompatibility complex class I (MHC I) molecules, and enabled a greater understanding of the dynamic nature of the immunopeptidome of normal and neoplastic cells. While the isolation of MHC I-associated peptides (MIPs) typically used mild acid elution (MAE) or immunoprecipitation (IP), limited information currently exists regarding their respective analytical merits...
March 6, 2018: Proteomics
Ida Hafstrand, Elien M Doorduijn, Renhua Sun, Anna Talyzina, Marjolein Sluijter, Sara Pellegrino, Tatyana Sandalova, Adil Doganay Duru, Thorbald van Hall, Adnane Achour
Human cancers frequently display defects in Ag processing and presentation allowing for immune evasion, and they therefore constitute a significant challenge for T cell-based immunotherapy. We have previously demonstrated that the antigenicity of tumor-associated Ags can be significantly enhanced through unconventional residue modifications as a novel tool for MHC class I (MHC-I)-based immunotherapy approaches. We have also previously identified a novel category of cancer neo-epitopes, that is, T cell epitopes associated with impaired peptide processing (TEIPP), that are selectively presented by MHC-I on cells lacking the peptide transporter TAP...
March 5, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Priyanka Chauhan, Wen S Sheng, Shuxian Hu, Sujata Prasad, James R Lokensgard
BACKGROUND: Peripheral neuropathy is currently the most common neurological complication in HIV-infected individuals, occurring in 35-50% of patients undergoing combination anti-retroviral therapy. Data have shown that distal symmetric polyneuropathy develops in mice by 6 weeks following infection with the LP-BM5 retrovirus mixture. Previous work from our laboratory has demonstrated that glial cells modulate antiviral T-cell effector responses through the programmed death (PD)-1: PD-L1 pathway, thereby limiting the deleterious consequences of unrestrained neuroinflammation...
March 5, 2018: Journal of Neuroinflammation
Anne C Knol, Jean-Michel Nguyen, Marie-Christine Pandolfino, Marc G Denis, Amir Khammari, Brigitte Dréno
Prognostic biomarkers for melanoma patients after lymph node resection are of clinical relevance and could thus enable the identification of patients who therefore would most benefit from adjuvant treatment. The aim of this work was to determine, using an in vitro model, whether immune-related biomarkers such as MHC-class I and II, melanoma associated antigens, IDO1 and PD-L1, could also be relevant to predict the risk of relapse of stage III melanoma patients after lymph node resection. We established tumor cell lines from metastatic lymph nodes of 50 melanoma patients...
March 5, 2018: Experimental Dermatology
Moein Farshchian, Maryam M Matin, Olivier Armant, Dirk Geerts, Mahtab Dastpak, Saeideh Nakhaei-Rad, Massoumeh Tajeran, Amir Jebelli, Mina Shahriyari, Monireh Bahrami, Ali Fallah, Vesal Yaghoobi, Mahdi Mirahmadi, Mohammad Reza Abbaszadegan, Ahmad Reza Bahrami
The self-renewal capacity of germline derived stem cells (GSCs) makes them an ideal source for research and use in clinics. Despite the presence of active gene network similarities between embryonic stem cells (ESCs) and GSCs, there are unanswered questions regarding the roles of evolutionary conserved genes in GSCs. To determine the reprogramming potential of germ cell- specific genes, we designed a polycistronic gene cassette expressing Stella, Oct4 and Nanos2 in a lentiviral-based vector. Deep transcriptome analysis showed the activation of a set of pluripotency and germ-cell-specific markers and the downregulation of innate immune system...
March 1, 2018: Cytokine
Shinsuke Kanekiyo, Shoichi Hazama, Hiroko Takenouchi, Masao Nakajima, Yoshitaro Shindo, Hiroto Matsui, Yukio Tokumitsu, Shinobu Tomochika, Ryouichi Tsunedomi, Yoshihiro Tokuhisa, Michihisa Iida, Kazuhiko Sakamoto, Nobuaki Suzuki, Shigeru Takeda, Shigeru Yamamoto, Shigefumi Yoshino, Kiyotaka Okuno, Keiko Udaka, Yutaka Kawakami, Satoko Matsueda, Kyogo Ito, Hiroaki Nagano
Cancer vaccines have been developed as a new therapeutic approach, however, their clinical benefit remains limited. We previously performed a phase II study for advanced colorectal cancer (CRC) using five human leukocyte antigen (HLA-A*24:02)-restricted peptides derived from kinase of the outer chloroplast membrane 1, translocase of outer mitochondrial membrane 34 (TOMM34), ring finger protein 43 (RNF43), vascular endothelial growth factor receptor 1 (VEGFR1) and VEGFR2. In the present study the relationship between overall survival (OS) and several biomarkers, including cytotoxic T lymphocyte (CTL) and immunoglobulin G (IgG) responses to these five peptides, was investigated...
March 1, 2018: Oncology Reports
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