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Self antigen

Tomotaka Kawayama, Takashi Kinoshita, Kazuko Matsunaga, Yoshiko Naito, Jun Sasaki, Yoshikazu Tominaga, Tomoaki Hoshino
Asthma is an allergic disease characterized by chronic airway inflammation, airway hyperresponsiveness (AHR), reversibility and remodeling. Inhaled corticosteroids (ICS) are effective in many patients with asthma. However, ICS are a controlling, but not but curative treatment, and there are still many patients with refractory and difficult-to-treat asthma. The evaluation of airway inflammation by induced sputum, non-specific AHR by methacholine, and asthmatic reactions by specific allergen challenge techniques are useful not only to investigate the pathogenesis of asthma but also to help develop new drugs for asthma management...
March 16, 2018: Kurume Medical Journal
Jessica Da Gama Duarte, Sagun Parakh, Miles C Andrews, Katherine Woods, Anupama Pasam, Candani Tutuka, Simone Ostrouska, Jonathan M Blackburn, Andreas Behren, Jonathan Cebon
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced melanoma. The first ICI to demonstrate clinical benefit, ipilimumab, targets cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4); however, the long-term overall survival is just 22%. More than 40 years ago intralesional (IL) bacillus Calmette-Guérin (BCG), a living attenuated strain of Mycobacterium bovis , was found to induce tumor regression by stimulating cell-mediated immunity following a localized and self-limiting infection...
2018: Frontiers in Immunology
Robert A LaMothe, Pallavi N Kolte, Trinh Vo, Joseph D Ferrari, Tracy C Gelsinger, Jodie Wong, Victor T Chan, Sinthia Ahmed, Aditi Srinivasan, Patrick Deitemeyer, Roberto A Maldonado, Takashi K Kishimoto
T cells reacting to self-components can promote tissue damage when escaping tolerogenic control mechanisms which may result in autoimmune disease. The current treatments for these disorders are not antigen (Ag) specific and can compromise host immunity through chronic suppression. We have previously demonstrated that co-administration of encapsulated or free Ag with tolerogenic nanoparticles (tNPs) comprised of biodegradable polymers that encapsulate rapamycin are capable of inhibiting Ag-specific transgenic T cell proliferation and inducing Ag-specific regulatory T cells (Tregs)...
2018: Frontiers in Immunology
Andrea Mencarelli, Hanif Javanmard Khameneh, Jan Fric, Maurizio Vacca, Sary El Daker, Baptiste Janela, Jing Ping Tang, Sabrina Nabti, Akhila Balachander, Tong Seng Lim, Florent Ginhoux, Paola Ricciardi-Castagnoli, Alessandra Mortellaro
The intestinal immune system can respond to invading pathogens yet maintain immune tolerance to self-antigens and microbiota. Myeloid cells are central to these processes, but the signaling pathways that underlie tolerance versus inflammation are unclear. Here we show that mice lacking Calcineurin B in CD11chigh MHCII+ cells (Cnb1CD11c mice) spontaneously develop intestinal inflammation and are susceptible to induced colitis. In these mice, colitis is associated with expansion of T helper type 1 (Th1) and Th17 cell populations and a decrease in the number of FoxP3+ regulatory T (Treg) cells, and the pathology is linked to the inability of intestinal Cnb1-deficient CD11chigh MHCII+ cells to express IL-2...
March 16, 2018: Nature Communications
Erica J Brodie, Simona Infantino, Michael S Y Low, David M Tarlinton
Systemic lupus erythematosus (SLE) is a progressive autoimmune disease characterized by increased sensitivity to self-antigens, auto-antibody production, and systemic inflammation. B cells have been implicated in disease progression and as such represent an attractive therapeutic target. Lyn is a Src family tyrosine kinase that plays a major role in regulating signaling pathways within B cells as well as other hematopoietic cells. Its role in initiating negative signaling cascades is especially critical as exemplified by Lyn-/- mice developing an SLE-like disease with plasma cell hyperplasia, underscoring the importance of tightly regulating signaling within B cells...
2018: Frontiers in Immunology
Nicolle H R Litjens, Lotte van der Wagen, Jurgen Kuball, Jaap Kwekkeboom
Cytomegalovirus (CMV) infection can cause significant complications after transplantation, but recent emerging data suggest that CMV may paradoxically also exert beneficial effects in two specific allogeneic transplant settings. These potential benefits have been underappreciated and are therefore highlighted in this review. First, after allogeneic hematopoietic stem cell transplantation (HSCT) for acute myeloid leukemia (AML) using T-cell and natural killer (NK) cell-replete grafts, CMV reactivation is associated with protection from leukemic relapse...
2018: Frontiers in Immunology
Cheleka A M Mpande, One B Dintwe, Munyaradzi Musvosvi, Simbarashe Mabwe, Nicole Bilek, Mark Hatherill, Elisa Nemes, Thomas J Scriba
Background: Maintenance of long-lasting immunity is thought to depend on stem cell memory T cells (TSCM ), which have superior self-renewing capacity, longevity and proliferative potential compared with central memory (TCM ) or effector (TEFF ) T cells. Our knowledge of TSCM derives primarily from studies of virus-specific CD8+ TSCM . We aimed to determine if infection with Mycobacterium tuberculosis ( M. tb ), the etiological agent of tuberculosis, generates antigen-specific CD4+ TSCM and to characterize their functional ontology...
2018: Frontiers in Immunology
Minghua Zheng, Jie Jiang, Xiao Zhang, Nan Wang, Kaihang Wang, Qiong Li, Tingting Li, Qingshan Lin, Yingbin Wang, Hai Yu, Ying Gu, Jun Zhang, Shaowei Li, Ningshao Xia
Hepatitis E virus (HEV) is associated with acute hepatitis disease. Numerous truncated HEV capsid proteins have been successfully expressed using different expression systems. Among these, p495, a protein truncated at its N- and C-termini by 111 and 54 amino acids (aa), respectively (HEV ORF2 aa 112-606) can self-assemble into T = 1 virus-like particles (VLPs) when expressed by insect cells. A shorter p239 (aa 368-606) protein is a particulate antigen that we have previously used in our commercialized HEV vaccine, Hecolin...
March 12, 2018: Vaccine
Emma L Smith, Mark Peakman
Autoimmune and allergic diseases occur when an individual mounts an inappropriate immune response to a self-antigen or an innocuous environmental antigen. This triggers a pathogenic T-cell response resulting in damage to specific tissues and organs. In type 1 diabetes (T1D), this manifests as destruction of the insulin-secreting β cells, resulting in a life-long dependency on recombinant insulin. Modulation of the pathogenic T-cell response with antigen-specific peptide immunotherapy offers the potential to restore the immune homeostasis and prevent further tissue destruction...
2018: Frontiers in Immunology
Emilia Vendelova, Diyaaeldin Ashour, Patrick Blank, Florian Erhard, Antoine-Emmanuel Saliba, Ulrich Kalinke, Manfred B Lutz
Dendritic cells (DCs) are key directors of tolerogenic and immunogenic immune responses. During the steady state, DCs maintain T cell tolerance to self-antigens by multiple mechanisms including inducing anergy, deletion, and Treg activity. All of these mechanisms help to prevent autoimmune diseases or other hyperreactivities. Different DC subsets contribute to pathogen recognition by expression of different subsets of pattern recognition receptors, including Toll-like receptors or C-type lectins. In addition to the triggering of immune responses in infected hosts, most pathogens have evolved mechanisms for evasion of targeted responses...
2018: Frontiers in Immunology
Clifford M Csizmar, Jacob Petersburg, Alexander Hendricks, Lawrence A Stern, Benjamin J Hackel, Carston R Wagner
Membrane-engineered cells displaying antigen-targeting ligands are useful as both scientific tools and clinical therapeutics. While genetically-encoded artificial receptors have proven efficacious, their scope remains limited as this approach is not amenable to all cell types and the modification is often permanent. Our group has developed a non-genetic method to rapidly, stably, and reversibly modify any cell membrane with a chemically self-assembled nanoring (CSAN) that can function as a prosthetic receptor...
March 14, 2018: Bioconjugate Chemistry
Taku Kuwabara, Yukihide Matsui, Fumio Ishikawa, Motonari Kondo
The adaptive immune system involves antigen-specific host defense mechanisms mediated by T and B cells. In particular, CD4⁺ T cells play a central role in the elimination of pathogens. Immunological tolerance in the thymus regulates T lymphocytes to avoid self-components, including induction of cell death in immature T cells expressing the self-reactive T-cell receptor repertoire. In the periphery, mature T cells are also regulated by tolerance, e.g., via induction of anergy or regulatory T cells. Thus, T cells strictly control intrinsic signal transduction to prevent excessive responses or self-reactions...
March 12, 2018: International Journal of Molecular Sciences
Valeria La Marca, Elena Gianchecchi, Alessandra Fierabracci
Type 1 diabetes (T1D) affects millions of people worldwide and is the prevalent form of all pediatric diabetes diagnoses. T1D is recognized to have an autoimmune etiology, since failure in specific self-tolerance mechanisms triggers immune reactions towards self-antigens and causes disease onset. Among all the different immunocytes involved in T1D etiopathogenesis, a relevant role of natural killer cells (NKs) is currently emerging. NKs represent the interface between innate and adaptive immunity; they intervene in the defense against infections and present, at the same time, typical features of the adaptive immune cells, such as expansion and generation of memory cells...
March 10, 2018: International Journal of Molecular Sciences
Kwok S Wun, Josephine F Reijneveld, Tan-Yun Cheng, Kristin Ladell, Adam P Uldrich, Jérôme Le Nours, Kelly L Miners, James E McLaren, Emma J Grant, Oscar L Haigh, Thomas S Watkins, Sara Suliman, Sarah Iwany, Judith Jimenez, Roger Calderon, Kattya L Tamara, Segundo R Leon, Megan B Murray, Jacob A Mayfield, John D Altman, Anthony W Purcell, John J Miles, Dale I Godfrey, Stephanie Gras, David A Price, Ildiko Van Rhijn, D Branch Moody, Jamie Rossjohn
The hallmark function of αβ T cell antigen receptors (TCRs) involves the highly specific co-recognition of a major histocompatibility complex molecule and its carried peptide. However, the molecular basis of the interactions of TCRs with the lipid antigen-presenting molecule CD1c is unknown. We identified frequent staining of human T cells with CD1c tetramers across numerous subjects. Whereas TCRs typically show high specificity for antigen, both tetramer binding and autoreactivity occurred with CD1c in complex with numerous, chemically diverse self lipids...
March 12, 2018: Nature Immunology
Hélène Carabin, Athanase Millogo, Helena A Ngowi, Cici Bauer, Veronique Dermauw, Assana Cissé Koné, Ida Sahlu, Alicia L Salvator, Pierre-Marie Preux, Télesphore Somé, Zékiba Tarnagda, Sarah Gabriël, Rabiou Cissé, Jean-Bosco Ouédraogo, Linda D Cowan, Marie-Paule Boncoeur-Martel, Pierre Dorny, Rasmané Ganaba
BACKGROUND: The effectiveness of drug-free interventions in controlling human cysticercosis is not well known. We aimed to estimate the effectiveness of a community-based educational intervention in reducing the frequency of human cysticercosis in Burkina Faso. METHODS: We did a cluster-randomised controlled trial between 2011 and 2014. 60 eligible villages from three provinces (Boulkiemdé, Sanguié, and Nayala) were randomly allocated to the intervention or control group...
April 2018: Lancet Global Health
Yujuan Chen, Fengjiao Yuan, Xian Jiang, Qing Lv, Na Luo, Changyang Gong, Chunting Wang, Li Yang, Gu He
Recently, tumor immunotherapy has achieved great progress in the treatment of hematological and solid neoplasms. The DC vaccines, KLH-conjugated vaccines or glycosylated peptide vaccines can efficiently induce immune responses against tumors. In the current study, we have discovered cholesteryl PADRE-EGFRvIII epitope-conjugated lipopeptide self-assembled micelles as a potential self-adjuvant vaccine against cutaneous melanoma. The lipopeptide vaccines were synthesized using a standard solid phase peptide synthesis method, and these vaccines could elicit both a humoral and a cellular immune response to EGFRvIII positive melanoma cells...
March 12, 2018: Biomaterials Science
Valery I Turobov, Alexey V Danilkovich, Alexei B Shevelev, Yulia K Biryukova, Natalia V Pozdniakova, Viatcheslav N Azev, Arkady N Murashev, Valery M Lipkin, Igor P Udovichenko
Peptide immunocortin sequence corresponds to the amino acid residues 11-20 of the variable part of human immunoglobulin G1 (IgG1) heavy chain. Since immunocortin was shown previously to inhibit phagocytosis in peritoneal macrophages and ConA-induced T-lymphocytes proliferation in culture, we suggested that immunocortin administering may be of use for patients with self-immune syndrome. Immunocortin in concentration 10 μM inhibited proliferation of both antigen (myelin)-induced and ConA-induced LN lymphocytes isolated from the lymph nodes of Dark Agouti (DA) rats immunized with chorda shear...
2018: Frontiers in Pharmacology
Visalini Nair-Shalliker, Albert Bang, Marianne Weber, David E Goldsbury, Michael Caruana, Jon Emery, Emily Banks, Karen Canfell, Dianne L O'Connell, David P Smith
Australia has one of the highest incidence rates of prostate cancer (PC) worldwide, due in part to widespread prostate specific antigen (PSA) testing. We aimed to identify factors associated with PSA testing in Australian men without a diagnosis of prostate cancer or prior prostate disease. Participants were men joining the 45 and Up Study in 2006-2009, aged ≥45 years at recruitment. Self-completed questionnaires were linked to cancer registrations, hospitalisations, health services data and deaths. Men with a history of PC, radical prostatectomy or a "monitoring" PSA test for prostate disease were excluded...
March 9, 2018: Scientific Reports
Esteban Arrieta-Bolaños, Pietro Crivello, Maximilian Metzing, Thuja Meurer, Müberra Ahci, Julie Rytlewski, Marissa Vignali, Erik Yusko, Peter van Balen, Peter A Horn, J H Frederik Falkenburg, Katharina Fleischhauer
T cell alloreactivity is mediated by a self-human leukocyte antigen (HLA)-restricted T cell receptor (TCR) repertoire able to recognize both structurally similar and dissimilar allogeneic HLA molecules (i.e., differing by a single or several amino acids in their peptide-binding groove). We hypothesized that thymic selection on self-HLA molecules could have an indirect impact on the size and diversity of the alloreactive response. To test this possibility, we used TCR Vβ immunophenotyping and immunosequencing technology in a model of alloreactivity between self-HLA selected T cells and allogeneic HLA-DPB1 (DPB1) differing from self-DPB1*04:02 by a single (DPB1*02:01) or several (DPB1*09:01) amino acids in the peptide-binding groove...
2018: Frontiers in Immunology
Ming-Wei Chien, Shin-Huei Fu, Chao-Yuan Hsu, Yu-Wen Liu, Huey-Kang Sytwu
Glycosylation is a ubiquitous posttranslational modification of proteins that occurs in the endoplasmic reticulum/Golgi. N -glycans and mucin-type O -glycans are achieved via a series of glycohydrolase- and glycosyltransferase-mediated reactions. Glycosylation modulates immune responses by regulating thymocyte development and T helper cell differentiation. Autoimmune diseases result from an abnormal immune response by self-antigens and subsequently lead to the destruction of the target tissues. The modification of N -glycans has been studied in several animal models of T-cell-mediated autoimmune diseases...
March 8, 2018: International Journal of Molecular Sciences
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