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https://www.readbyqxmd.com/read/29754112/mr1-antigen-presentation-to-mait-cells-new-ligands-diverse-pathways
#1
REVIEW
Hamish Eg McWilliam, Jose A Villadangos
The major histocompatibility complex class I-related molecule MR1 is the only antigen (Ag) presenting molecule that captures and displays vitamin B-derived metabolites that are unique to a wide array of microbes. Presentation of these metabolite Ag at the cell surface activates mucosal-associated invariant T (MAIT) cells, a highly abundant innate-like T cell population, and represents a recently-described mechanism used by the mammalian immune system to sense pathogenic or commensal microbes. Our understanding of the cell biology of how MR1 accomplishes this unique task is still evolving, but recent advances are allowing a general picture to emerge...
May 10, 2018: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29749611/proteomic-definition-of-human-mucosal-associated-invariant-t-cells-determines-their-unique-molecular-effector-phenotype
#2
Björn Bulitta, Werner Zuschratter, Isabel Bernal, Dunja Bruder, Frank Klawonn, Martin von Bergen, Henrikus Stephanus Paulus Garritsen, Lothar Jänsch
Mucosal-associated invariant T cells (MAIT) constitute the most abundant anti-bacterial CD8+ T cell population in humans. MR1/TCR-activated MAIT cells were reported to organize cytotoxic and innate-like responses but knowledge about their molecular effector phenotype is still fragmentary. Here, we have examined the functional inventory of human MAIT cells (CD3+Vα7.2+CD161+) in comparison with those from conventional non-MAIT CD8+ T cells (cCD8+ ) and NK cells. Quantitative mass spectrometry characterized 5500 proteins of primary MAIT cells and identified 160 and 135 proteins that discriminate them from cCD8+ T cells and NK cells donor-independently...
May 11, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29731053/severely-impaired-control-of-bacterial-infections-in-a-patient-with-cystic-fibrosis-defective-in-mucosal-associated-invariant-t-cells
#3
Terezia Pincikova, Dominic Paquin-Proulx, Markus Moll, Malin Flodström-Tullberg, Lena Hjelte, Johan K Sandberg
Here we report a unique case of a patient with cystic fibrosis characterized by severely impaired control of bacterial respiratory infections. This patient's susceptibility to such infections was much worse than expected from a cystic fibrosis clinical perspective, and he died at age 22 years despite extensive efforts and massive use of antibiotics. We found that this severe condition was associated with a near-complete deficiency in circulating mucosal-associated invariant T (MAIT) cells as measured at several time points...
May 2018: Chest
https://www.readbyqxmd.com/read/29668066/mait-cell-mediated-cytotoxicity-roles-in-host-defense-and-therapeutic-potentials-in-infectious-diseases-and-cancer
#4
REVIEW
Patrick T Rudak, Joshua Choi, S M Mansour Haeryfar
Mucosa-associated invariant T (MAIT) cells are unconventional, innate-like T lymphocytes that sense the presence of MHC-related protein 1 (MR1)-restricted ligands and select inflammatory cues. Consequently, they release potent immunomodulatory mediators, including IFN-γ, TNF-α, and/or IL-17. MAIT cells can also be viewed as killer cells. They display several NK cell-associated receptors, carry granules containing cytotoxic effector molecules, and swiftly upregulate perforin and granzymes upon activation. Accordingly, MAIT cells are capable of lysing MR1-expressing cells infected with a variety of pathogenic bacteria in in vitro settings and may also mount cytotoxic responses during microbial infections in vivo...
April 18, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29656544/an-overview-on-the-identification-of-mait-cell-antigens
#5
Lars Kjer-Nielsen, Alexandra J Corbett, Zhenjun Chen, Ligong Liu, Jeffrey Y W Mak, Dale I Godfrey, Jamie Rossjohn, David P Fairlie, James McCluskey, Sidonia B G Eckle
Mucosal Associated Invariant T (MAIT) cells are restricted by the monomorphic MHC class I-like molecule, MHC-related protein-1 (MR1). Until 2012, the origin of the MAIT cell antigens (Ags) was unknown, although it was established that MAIT cells could be activated by a broad range of bacteria and yeasts, possibly suggesting a conserved Ag. Using a combination of protein chemistry, mass spectrometry, cellular biology, structural biology and chemistry, we discovered MAIT cell ligands derived from folic acid (vitamin B9) and from an intermediate in the microbial biosynthesis of riboflavin (vitamin B2)...
April 14, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29629900/recipient-mucosal-associated-invariant-t-cells-control-gvhd-within-the-colon
#6
Antiopi Varelias, Mark D Bunting, Kate L Ormerod, Motoko Koyama, Stuart D Olver, Jasmin Straube, Rachel D Kuns, Renee J Robb, Andrea S Henden, Leanne Cooper, Nancy Lachner, Kate H Gartlan, Olivier Lantz, Lars Kjer-Nielsen, Jeffrey Yw Mak, David P Fairlie, Andrew D Clouston, James McCluskey, Jamie Rossjohn, Steven W Lane, Philip Hugenholtz, Geoffrey R Hill
Mucosal-associated invariant T (MAIT) cells are a unique innate-like T cell subset that responds to a wide array of bacteria and yeast through recognition of riboflavin metabolites presented by the MHC class I-like molecule MR1. Here, we demonstrate using MR1 tetramers that recipient MAIT cells are present in small but definable numbers in graft-versus-host disease (GVHD) target organs and protect from acute GVHD in the colon following bone marrow transplantation (BMT). Consistent with their preferential juxtaposition to microbial signals in the colon, recipient MAIT cells generate large amounts of IL-17A, promote gastrointestinal tract integrity, and limit the donor alloantigen presentation that in turn drives donor Th1 and Th17 expansion specifically in the colon after BMT...
April 9, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29522194/neutralization-of-cd40-ligand-costimulation-promotes-bone-formation-and-accretion-of-vertebral-bone-mass-in-mice
#7
Susanne Roser-Page, Tatyana Vikulina, Kanglun Yu, Meghan E McGee-Lawrence, M Neale Weitzmann
Objective: Immunosuppressive biologics are used in the management of RA and additional immunomodulators are under investigation including modulators of the CD40/CD40 ligand (CD40L) costimulation pathway. Tampering with immune function can have unanticipated skeletal consequences due to disruption of the immuno-skeletal interface, a nexus of shared cells and cytokine effectors serving discrete functions in both immune and skeletal systems. In this study, we examined the effect of MR1, a CD40L neutralizing antibody, on physiological bone remodelling in healthy mice...
March 7, 2018: Rheumatology
https://www.readbyqxmd.com/read/29515123/enumeration-functional-responses-and-cytotoxic-capacity-of-mait-cells-in-newly-diagnosed-and-relapsed-multiple-myeloma
#8
Nicholas A Gherardin, Liyen Loh, Lorenztino Admojo, Alexander J Davenport, Kelden Richardson, Amy Rogers, Phillip K Darcy, Misty R Jenkins, H Miles Prince, Simon J Harrison, Hang Quach, David P Fairlie, Katherine Kedzierska, James McCluskey, Adam P Uldrich, Paul J Neeson, David S Ritchie, Dale I Godfrey
Mucosal-associated invariant T (MAIT) cells are T cells that recognise vitamin-B derivative Ag presented by the MHC-related-protein 1 (MR1) antigen-presenting molecule. While MAIT cells are highly abundant in humans, their role in tumour immunity remains unknown. Here we have analysed the frequency and function of MAIT cells in multiple myeloma (MM) patients. We show that MAIT cell frequency in blood is reduced compared to healthy adult donors, but comparable to elderly healthy control donors. Furthermore, there was no evidence that MAIT cells accumulated at the disease site (bone marrow) of these patients...
March 7, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29511377/differences-in-c-type-lectin-receptors-and-their-adaptor-molecules-in-the-peritoneal-fluid-of-patients-with-endometriosis-and-gynecologic-cancers
#9
Seung Geun Yeo, Yong Sung Won, Sang Hoon Kim, Dong Choon Park
Endometriosis, although not malignant, has clinically demonstrated properties of invasiveness and metastasis. The pathogenesis of endometriosis, however, has not yet been elucidated. The immunological differences between endometriosis and malignant gynecologic tumors were analyzed by assessing C-type lectin receptors, which are associated with innate immunity, and immunoglobulin secretion, which is associated with B cell adaptive immunity, in the peritoneal fluid of these patients. Peritoneal fluid samples were obtained from 42 patients with benign masses (control group), 38 with endometriosis, and 43 with gynecologic (ovarian, uterine, and cervical) cancers...
2018: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29507084/interleukin-18-is-critical-for-mucosa-associated-invariant-t-cell-gamma-interferon-responses-to-francisella-species-in-vitro-but-not-in-vivo
#10
Eric Jesteadt, Irma Zhang, Huifeng Yu, Anda Meierovics, Wei-Jen Chua Yankelevich, Siobhan Cowley
Mucosa-associated invariant T (MAIT) cells are a subset of innate T cells that express a semi-invariant Vα chain paired with limited Vβ chains. MAIT cells are activated by riboflavin metabolite derivatives presented by the nonpolymorphic major histocompatibility complex class I (MHC-I)-like molecule MR1. The precise mechanisms required to activate MAIT cells are an area of intense interest. Here we used two closely related intracellular pathogens with distinct inflammasome activation phenotypes to probe the role of innate cytokines in MAIT cell activation...
May 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29470597/mucosa-associated-invariant-t-cells-in-malignancies-a-faithful-friend-or-formidable-foe
#11
REVIEW
S M Mansour Haeryfar, Christopher R Shaler, Patrick T Rudak
Mucosa-associated invariant T (MAIT) cells are a subset of innate-like T lymphocytes known for their ability to respond to MHC-related protein 1 (MR1)-restricted stimuli and select cytokine signals. They are abundant in humans and especially enriched in mucosal layers, common sites of neoplastic transformation. MAIT cells have been found within primary and metastatic tumors. However, whether they promote malignancy or contribute to anticancer immunity is unclear. On the one hand, MAIT cells produce IL-17A in certain locations and under certain circumstances, which could in turn facilitate neoangiogenesis, intratumoral accumulation of immunosuppressive cell populations, and cancer progression...
February 22, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29451704/mait-cells-and-microbial-immunity
#12
REVIEW
Erin W Meermeier, Melanie J Harriff, Elham Karamooz, David M Lewinsohn
Mucosal-associated invariant T (MAIT) cells, the most abundant T-cell subset in humans, are increasingly being recognized for their importance in microbial immunity. MAIT cells accumulate in almost every mucosal tissue examined, including the lung, liver and intestinal tract, where they can be activated through T-cell receptor (TCR) triggering as well as cytokine stimulation in response to a host of microbial products. In this review, we specifically discuss MAIT cell responses to bacterial and fungal infections, with a focus on responses that are both MR1-dependent and -independent, the evidence for diversity in MAIT TCR usage in response to discrete microbial products, protective immunity induced by MAIT cells, and MAIT cell antimicrobial functions in the context of these infections...
February 16, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29437263/human-blood-mait-cell-subsets-defined-using-mr1-tetramers
#13
Nicholas A Gherardin, Michael Nt Souter, Hui-Fern Koay, Kirstie M Mangas, Torsten Seemann, Timothy P Stinear, Sidonia Bg Eckle, Stuart P Berzins, Yves d'Udekem, Igor E Konstantinov, David P Fairlie, David S Ritchie, Paul J Neeson, Daniel G Pellicci, Adam P Uldrich, James McCluskey, Dale I Godfrey
Mucosal-associated invariant T (MAIT) cells represent up to 10% of circulating human T cells. They are usually defined using combinations of non-lineage-specific (surrogate) markers such as anti-TRAV1-2, CD161, IL-18Rα and CD26. The development of MR1-Ag tetramers now permits the specific identification of MAIT cells based on T-cell receptor specificity. Here, we compare these approaches for identifying MAIT cells and show that surrogate markers are not always accurate in identifying these cells, particularly the CD4+ fraction...
February 13, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29434453/faecal-calprotectin-and-magnetic-resonance-imaging-in-detecting-crohn-s-disease-endoscopic-postoperative-recurrence
#14
Pierre Baillet, Guillaume Cadiot, Marion Goutte, Felix Goutorbe, Hedia Brixi, Christine Hoeffel, Christophe Allimant, Maud Reymond, Hélène Obritin-Guilhen, Benoit Magnin, Gilles Bommelaer, Bruno Pereira, Constance Hordonneau, Anthony Buisson
AIM: To assess magnetic resonance imaging (MRI) and faecal calprotectin to detect endoscopic postoperative recurrence in patients with Crohn's disease (CD). METHODS: From two tertiary centers, all patients with CD who underwent ileocolonic resection were consecutively and prospectively included. All the patients underwent MRI and endoscopy within the first year after surgery or after the restoration of intestinal continuity [median = 6 mo (5.0-9.3)]. The stools were collected the day before the colonoscopy to evaluate faecal calprotectin level...
February 7, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29423939/human-mait-cells-show-metabolic-quiescence-with-rapid-glucose-dependent-upregulation-of-granzyme-b-upon-stimulation
#15
Madeleine E Zinser, Andrew J Highton, Ayako Kurioka, Barbara Kronsteiner, Joachim Hagel, Tianqi Leng, Emanuele Marchi, Chansavath Phetsouphanh, Chris B Willberg, Susanna J Dunachie, Paul Klenerman
Mucosal-associated invariant T (MAIT) cells are a well-characterized innate-like T cell population abundant in the human liver, peripheral tissues and blood. MAIT cells serve in the first line of defense against infections, through engagement of their T cell receptor, which recognizes microbial metabolites presented on MR1, and through cytokine-mediated triggering. Typically, they show a quiescent memory phenotype but can undergo rapid upregulation of effector functions including cytolysis upon stimulation...
February 9, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29405379/mucosal-associated-invariant-t-cells-in-autoimmune-and-immune-mediated-diseases
#16
REVIEW
Ophélie Rouxel, Agnès Lehuen
Autoimmune and inflammatory diseases have complex etiologies not fully understood. Both innate and adaptive immune cells are involved in the pathogenesis of these diseases. Mucosal-associated invariant T (MAIT) cells express an invariant TCRα chain (Vα7.2-Jα33 in humans and Vα19-Jα33 in mice) and recognize the conserved MHC-I-related molecule MR1 presenting bacterial metabolites derived from the synthesis of vitamin B. MAIT cells harbor tissue homing properties and produce inflammatory cytokines, suggesting that MAIT cells may play a key role in autoimmune and inflammatory diseases...
February 6, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29401462/synthesis-stabilization-and-characterization-of-the-mr1-ligand-precursor-5-amino-6-d-ribitylaminouracil-5-a-ru
#17
Kelin Li, Charles K Vorkas, Ashutosh Chaudhry, Donielle L Bell, Richard A Willis, Alexander Rudensky, John D Altman, Michael S Glickman, Jeffrey Aubé
Mucosal-associated invariant T (MAIT) cells are an abundant class of innate T cells restricted by the MHC I-related molecule MR1. MAIT cells can recognize bacterially-derived metabolic intermediates from the riboflavin pathway presented by MR1 and are postulated to play a role in innate antibacterial immunity through production of cytokines and direct bacterial killing. MR1 tetramers, typically stabilized by the adduct of 5-amino-6-D-ribitylaminouracil (5-A-RU) and methylglyoxal (MeG), are important tools for the study of MAIT cells...
2018: PloS One
https://www.readbyqxmd.com/read/29393543/mucosal-associated-invariant-t-cell-receptor-recognition-of-small-molecules-presented-by-mr1
#18
REVIEW
Wael Awad, Jérôme Le Nours, Lars Kjer-Nielsen, James McCluskey, Jamie Rossjohn
The major histocompatibility complex (MHC) class-I related molecule MR1 is a monomorphic and evolutionary conserved antigen (Ag)-presenting molecule that shares the overall architecture of MHC-I and CD1 proteins. However, in contrast to MHC-I and the CD1 family that present peptides and lipids, respectively, MR1 specifically presents small organic molecules. During microbial infection of mammalian cells, MR1 captures and presents vitamin B precursors, derived from the microbial biosynthesis of riboflavin, on the surface of antigen-presenting cells...
February 2, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29378910/mucosal-associated-invariant-t-cells-augment-immunopathology-and-gastritis-in-chronic-helicobacter-pylori-infection
#19
Criselle D'Souza, Troi Pediongco, Huimeng Wang, Jean-Pierre Y Scheerlinck, Lyudmila Kostenko, Robyn Esterbauer, Andrew W Stent, Sidonia B G Eckle, Bronwyn S Meehan, Richard A Strugnell, Hanwei Cao, Ligong Liu, Jeffrey Y W Mak, George Lovrecz, Louis Lu, David P Fairlie, Jamie Rossjohn, James McCluskey, Alison L Every, Zhenjun Chen, Alexandra J Corbett
Mucosal-associated invariant T (MAIT) cells produce inflammatory cytokines and cytotoxic granzymes in response to by-products of microbial riboflavin synthesis. Although MAIT cells are protective against some pathogens, we reasoned that they might contribute to pathology in chronic bacterial infection. We observed MAIT cells in proximity to Helicobacter pylori bacteria in human gastric tissue, and so, using MR1-tetramers, we examined whether MAIT cells contribute to chronic gastritis in a mouse H. pylori SS1 infection model...
March 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29363173/mait-cells-an-historical-and-evolutionary-perspective
#20
REVIEW
Olivier Lantz, François Legoux
In humans, MAIT cells represent the most abundant T-cell subset reacting against bacteria. MAIT cells belong to the evolutionarily conserved family of "preset" T cells that includes also NKT cells. Both subsets are selected by double positive thymocytes leading to common features such as PLZF expression. Preset T cells correspond to subsets prepositioned in specific tissue locations with preprogrammed versatile effector functions such as antimicrobial functions and possibly also metabolic control and tissue repair activity...
December 27, 2017: Immunology and Cell Biology
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