A Genome-wide multidimensional RNAi screen reveals pathways controlling MHC class II antigen presentation

Cell
Petra PaulJacques Neefjes

Abstract

MHC class II molecules (MHC-II) present peptides to T helper cells to facilitate immune responses and are strongly linked to autoimmune diseases. To unravel processes controlling MHC-II antigen presentation, we performed a genome-wide flow cytometry-based RNAi screen detecting MHC-II expression and peptide loading followed by additional high-throughput assays. All data sets were integrated to answer two fundamental questions: what regulates tissue-specific MHC-II transcription, and what controls MHC-II transport in dendritic cells? MHC-II transcription was controlled by nine regulators acting in feedback networks with higher-order control by signaling pathways, including TGFβ. MHC-II transport was controlled by the GTPase ARL14/ARF7, which recruits the motor myosin 1E via an effector protein ARF7EP. This complex controls movement of MHC-II vesicles along the actin cytoskeleton in human dendritic cells (DCs). These genome-wide systems analyses have thus identified factors and pathways controlling MHC-II transcription and transport, defining targets for manipulation of MHC-II antigen presentation in infection and autoimmunity.

References

Sep 4, 2012·Immunologic Research·Francesca Alvarez-CalderonJames DeGregori
Nov 30, 2012·Nature Reviews. Cancer·Geneviève Deblois, Vincent Giguère
Nov 15, 2011·Nature Reviews. Immunology·Jacques NeefjesOddmund Bakke
Oct 26, 2011·Nature Reviews. Immunology·Andrew ChowMiriam Merad
Jan 8, 2014·Current Allergy and Asthma Reports·Katy C LiuRichard M Davis
Jul 2, 2014·Immunology and Cell Biology·Kine M K SandTone F Gregers
Nov 28, 2012·Current Opinion in Immunology·Jessica M MoffatJosé A Villadangos
Oct 15, 2011·Developmental and Comparative Immunology·Michael F CriscitielloMartin F Flajnik
Sep 29, 2011·Wiley Interdisciplinary Reviews. RNA·Stephanie E Mohr, Norbert Perrimon
Nov 7, 2012·Traffic·Adriana R MantegazzaMichael S Marks
Dec 3, 2013·European Journal of Immunology·Sébastien WälchliTone F Gregers
Jul 22, 2014·Wiley Interdisciplinary Reviews. RNA·Clément Chapat, Laura Corbo
Jan 1, 2013·Results in Immunology·Marie-Claude Bourgeois-DaigneaultJacques Thibodeau
Sep 17, 2011·Immunology Letters·Barbara PlatzerEdda Fiebiger
Apr 1, 2015·Brain : a Journal of Neurology·Marvin M van LuijnRogier Q Hintzen
Feb 22, 2014·Current Opinion in Immunology·Sander I van KasterenJacques Neefjes
Aug 28, 2012·Immunity·Christopher D Dupont, Christopher A Hunter
Dec 4, 2012·Molecular Immunology·Malgorzata A Garstka, Jacques Neefjes
Nov 10, 2012·Molecular Immunology·Ruud H WijdevenJacques Neefjes
Oct 30, 2012·Molecular Immunology·Juan J García-VallejoYvette van Kooyk
Feb 28, 2015·Nature Reviews. Immunology·Paul A Roche, Kazuyuki Furuta
Mar 19, 2014·Seminars in Cell & Developmental Biology·Paul A Gleeson
Dec 3, 2014·Immunology Letters·Cornelis J M MeliefI Jolanda M de Vries
Sep 6, 2014·Frontiers in Genetics·Yo-Taro ShiraiTadashi Yamamoto
Apr 27, 2016·Current Opinion in Immunology·Katherine S Forsyth, Laurence C Eisenlohr
Feb 26, 2016·Annual Review of Immunology·Emil R UnanueJacques Neefjes
Jun 7, 2016·Best Practice & Research. Clinical Obstetrics & Gynaecology·Han ZhaoZi-Jiang Chen
Jun 21, 2016·Immunological Reviews·Marine BretouAna-Maria Lennon-Duménil
Aug 10, 2016·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Marta UklejaJorge Cuellar
Sep 12, 2016·Trends in Immunology·Kenneth L RockJacques Neefjes
Jan 11, 2017·The Journal of Cell Biology·Bradlee NelmsWayne Lencer
Apr 9, 2014·Journal of Biomolecular Screening·Shantanu SinghAuguste Genovesio
Jun 15, 2018·Traffic·Birol Cabukusta, Jacques Neefjes
Mar 2, 2019·Journal of Leukocyte Biology·Daniel Alberto Girón-PérezLeopoldo Santos-Argumedo
Dec 23, 2018·Annals of the Rheumatic Diseases·Marialbert Acosta-HerreraJavier Martin
Nov 22, 2012·British Journal of Cancer·D J Mahoney, D F Stojdl

Citations

Mar 15, 1985·International Journal of Cancer. Journal International Du Cancer·C VennegoorP Rümke
Jan 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·H K Ziegler, Emil R Unanue
Jun 29, 1995·Nature·V S SloanD M Zaller
Nov 1, 1996·The Journal of Cell Biology·R WubboltsJacques Neefjes
Sep 1, 1999·Proceedings of the National Academy of Sciences of the United States of America·M GromméJacques Neefjes
Jun 6, 2000·Journal of Biomolecular Screening·J H ZhangK R Oldenburg
Jun 18, 2003·Cell·Yigong Shi, Joan Massagué
May 1, 2004·Traffic·Miguel C Seabra, Evelyne Coudrier
Jul 3, 2004·Genome Research·Frédéric CollandJean-Michel Gauthier
Dec 2, 2004·Nature Reviews. Genetics·Roger HortonStephan Beck
Oct 4, 2005·Nature Reviews. Immunology·Walter ReithJean-Marc Waldburger
Feb 21, 2006·Nature·J Magarian Blander, Ruslan Medzhitov
Jan 30, 2007·FEBS Letters·Mira KrendelMark S Mooseker
Mar 29, 2007·The Journal of Cell Biology·Fulvia VascottoAna-Maria Lennon-Duménil
May 25, 2007·European Journal of Immunology·Akihito ImaiNoriyuki Sato
Aug 19, 2007·The Journal of Biological Chemistry·Cataldo SchietromaCameron B Gundersen
Jan 5, 2008·Annual Review of Immunology·Mary E KeirArlene H Sharpe
Feb 5, 2008·The Journal of Biological Chemistry·Lilien N VoongDrew E Cressman
Apr 5, 2008·European Journal of Immunology·Jacques ThibodeauViktor Steimle
Sep 12, 2008·The EMBO Journal·Mariella VicinanzaMaria Antonietta De Matteis
Feb 4, 2009·Proceedings of the National Academy of Sciences of the United States of America·Thouis R JonesDavid M Sabatini

Related Concepts

Pathologic Cytolysis
Establishment and Maintenance of Localization
Real-Time Polymerase Chain Reaction
Genome-Wide Association Study
Monoclonal Antibodies
Hygromycin A
Immune Response
Monoclonal antibodies, antineoplastic
Protease Inhibitors [MoA]
Flow Cytometry

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