Volume 21 Issue 4, April 2020

Volume 21 Issue 4

MAIT cell antigen recognition

Mucosa-associated invariant T (MAIT) cells recognize vitamin B metabolites presented by the molecule MR1. Rossjohn and colleagues generate multiple altered metabolite ligands and determine their structures in the context of MR1 and the TCR to develop a generalized framework for MAIT cell antigen recognition.

See Awad et al.

Image: Erica Tandori. Cover Design: Erin Dewalt.

Obituary

Research Highlights

News & Views

  • News & Views |

    Comprehensive analysis of CD8+ T cell populations specific to cytomegalovirus reveals that the evolution of the T cell antigen receptor repertoire during chronic infections is characterized by the expansion of low-affinity clones.

    • Anke Redeker
    •  & Ramon Arens
  • News & Views |

    The ubiquitin-editing enzyme A20 has a pivotal role in restricting autoimmune and inflammatory responses. New studies suggest that A20 prevents inflammatory diseases using a non-catalytic mechanism involving ubiquitin binding.

    • Shao-Cong Sun
  • News & Views |

    γδ T cells are critical contributors to tissue homeostasis. Recent research identifies an unexpected role for γδ T cell–derived IL-17F in promoting sympathetic innervation and tissue thermogenesis through the induction of the cytokine TGF-β in adipose cells.

    • Maria Ciofani

Review Articles

  • Review Article |

    Turley and Krishnamurty review new insights into lymph node stromal cells, a heterogeneous cell population that serves distinct functions during development, in maintaining lymphocyte homeostasis, and in coordinating immune responses.

    • Akshay T. Krishnamurty
    •  & Shannon J. Turley

Letters

  • Letter |

    van Loo and colleagues provide insights into the action of the anti-inflammatory protein A20. The ZnF7 and ZnF4 ubiquitin-binding domains of A20 are both required to suppress inflammatory signaling and cell death; however, these zinc fingers operate via distinct mechanisms.

    • Arne Martens
    • , Dario Priem
    • , Esther Hoste
    • , Jessica Vetters
    • , Sofie Rennen
    • , Leen Catrysse
    • , Sofie Voet
    • , Laura Deelen
    • , Mozes Sze
    • , Hanna Vikkula
    • , Karolina Slowicka
    • , Tino Hochepied
    • , Kalliopi Iliaki
    • , Andy Wullaert
    • , Sophie Janssens
    • , Mohamed Lamkanfi
    • , Rudi Beyaert
    • , Marietta Armaka
    • , Mathieu J. M. Bertrand
    •  & Geert van Loo

Articles

  • Article |

    Monticelli and colleagues analyze primary human CD4+ T cells to interrogate gene expression regulatory pathways that distinguish GM-CSF+ pathogenic programs from noninflammatory programs. They identify the transcriptional repressor BHLHE40 as an enforcer of proinflammatory gene expression by suppressing the NF-κB inhibitor miR-146a and the RNase ZC3H12D.

    • Stefan Emming
    • , Niccolò Bianchi
    • , Sara Polletti
    • , Chiara Balestrieri
    • , Cristina Leoni
    • , Sara Montagner
    • , Michele Chirichella
    • , Nicolas Delaleu
    • , Gioacchino Natoli
    •  & Silvia Monticelli
  • Article |

    Mucosal-associated invariant T (MAIT) cells recognize vitamin B metabolites presented by the molecule MR1. Rossjohn and colleagues generate multiple altered metabolite ligands and determine their structures in the context of MR1 and the TCR to develop a generalized framework for MAIT cell antigen recognition.

    • Wael Awad
    • , Geraldine J. M. Ler
    • , Weijun Xu
    • , Andrew N. Keller
    • , Jeffrey Y. W. Mak
    • , Xin Yi Lim
    • , Ligong Liu
    • , Sidonia B. G. Eckle
    • , Jérôme Le Nours
    • , James McCluskey
    • , Alexandra J. Corbett
    • , David P. Fairlie
    •  & Jamie Rossjohn
  • Article |

    Tissue-resident memory (TRM) cells are generally stably maintained in discrete tissues or organs. Masopust and colleagues show that TRM cells can reenter the circulation, and exhibit considerable plasticity, although they retain a proclivity to reestablish themselves in their tissue of origin.

    • Raissa Fonseca
    • , Lalit K. Beura
    • , Clare F. Quarnstrom
    • , Hazem E. Ghoneim
    • , Yiping Fan
    • , Caitlin C. Zebley
    • , Milcah C. Scott
    • , Nancy J. Fares-Frederickson
    • , Sathi Wijeyesinghe
    • , Emily A. Thompson
    • , Henrique Borges da Silva
    • , Vaiva Vezys
    • , Benjamin Youngblood
    •  & David Masopust
  • Article |

    The deubiquitinase A20 is a potent inhibitor of NF-κB signaling pathways. Ma and colleagues identify distinct roles for A20 ubiquitin-binding ZF4 and ZF7 domains, which exhibit different phenotypes upon mutation, but play synergistic roles in regulating inflammatory responses.

    • Bahram Razani
    • , Michael I. Whang
    • , Francis S. Kim
    • , Mary C. Nakamura
    • , Xiaofei Sun
    • , Rommel Advincula
    • , Jessie A. Turnbaugh
    • , Mihir Pendse
    • , Priscilia Tanbun
    • , Philip Achacoso
    • , Peter J. Turnbaugh
    • , Barbara A. Malynn
    •  & Averil Ma
  • Article |

    Busch and colleagues use single-cell and bulk TCR sequencing and structural affinity analyses of CMV-specific T cells to show that the immunodominance of high-affinity T cell clones declines during chronic infection with CMV, likely due to cellular senescence.

    • Kilian Schober
    • , Florian Voit
    • , Simon Grassmann
    • , Thomas R. Müller
    • , Joel Eggert
    • , Sebastian Jarosch
    • , Bianca Weißbrich
    • , Patrick Hoffmann
    • , Lisa Borkner
    • , Enzo Nio
    • , Lorenzo Fanchi
    • , Christopher R. Clouser
    • , Aditya Radhakrishnan
    • , Lorenz Mihatsch
    • , Philipp Lückemeier
    • , Justin Leube
    • , Georg Dössinger
    • , Ludger Klein
    • , Michael Neuenhahn
    • , Jennifer D. Oduro
    • , Luka Cicin-Sain
    • , Veit R. Buchholz
    •  & Dirk H. Busch
  • Article |

    PD-L1 on tumor cells exerts an important dampening effect on T cells via their expression of PD-1. Miller and colleagues find that PD-L1 ‘back-signaling’ into T cells and macrophages can also dampen immune responses within the tumor microenvironment.

    • Brian Diskin
    • , Salma Adam
    • , Marcelo F. Cassini
    • , Gustavo Sanchez
    • , Miguel Liria
    • , Berk Aykut
    • , Chandan Buttar
    • , Eric Li
    • , Belen Sundberg
    • , Ruben D. Salas
    • , Ruonan Chen
    • , Junjie Wang
    • , Mirhee Kim
    • , Mohammad Saad Farooq
    • , Susanna Nguy
    • , Carmine Fedele
    • , Kwan Ho Tang
    • , Ting Chen
    • , Wei Wang
    • , Mautin Hundeyin
    • , Juan A. Kochen Rossi
    • , Emma Kurz
    • , Muhammad Israr Ul Haq
    • , Jason Karlen
    • , Emma Kruger
    • , Zennur Sekendiz
    • , Dongling Wu
    • , Sorin A. A. Shadaloey
    • , Gillian Baptiste
    • , Gregor Werba
    • , Shanmugapriya Selvaraj
    • , Cynthia Loomis
    • , Kwok-Kin Wong
    • , Joshua Leinwand
    •  & George Miller
  • Article |

    Unanue and colleagues examine the immunopeptidome of pancreatic islets in non-obese diabetic (NOD) mice, which spontaneously develop autoimmune diabetes, to reveal the key features of a restricted component in the self-MHC-II peptidome that causes autoreactivity.

    • Xiaoxiao Wan
    • , Anthony N. Vomund
    • , Orion J. Peterson
    • , Alexander V. Chervonsky
    • , Cheryl F. Lichti
    •  & Emil R. Unanue

Resources

  • Resource |

    The pathobiological validity of mouse models of mycobacteria infection is sometimes questioned. O’Garra and colleagues demonstrate that mice share transcriptomic modules with active human tuberculosis and a characteristic type I IFN signature.

    • Lúcia Moreira-Teixeira
    • , Olivier Tabone
    • , Christine M. Graham
    • , Akul Singhania
    • , Evangelos Stavropoulos
    • , Paul S. Redford
    • , Probir Chakravarty
    • , Simon L. Priestnall
    • , Alejandro Suarez-Bonnet
    • , Eleanor Herbert
    • , Katrin D. Mayer-Barber
    • , Alan Sher
    • , Kaori L. Fonseca
    • , Jeremy Sousa
    • , Baltazar Cá
    • , Raman Verma
    • , Pranabashis Haldar
    • , Margarida Saraiva
    •  & Anne O’Garra

Amendments & Corrections