09 / 27 / 2021
The role of endocytic trafficking in antigen T Cell Receptor activation
Irini Evnouchidou, Vivien Caillens, Despoina Koumantou, Loredana Saveanu
Antigen T cell receptors (TCR) recognize antigenic peptides displayed by the major histocompatibility complex (pMHC) and play a critical role in T cell activation. The levels of TCR complexes at the cell surface, where signaling is initiated, depend on the balance between TCR synthesis, recycling and degradation. Cell surface TCR interaction with pMHC leads to receptor clustering and formation of a tight T cell-APC contact, the immune synapse, from which the activated TCR is internalized...
09 / 21 / 2021
mRNA vaccination of naive and COVID-19-recovered individuals elicits potent memory B cells that recognize SARS-CoV-2 variants
Aurélien Sokal, Giovanna Barba-Spaeth, Ignacio Fernández, Matteo Broketa,..., Pierre Bruhns, Felix A Rey, Jean-Claude Weill, Claude-Agnès Reynaud, Pascal Chappert, Matthieu Mahévas
In addition to serum immunoglobulins, memory B cell (MBC) generation against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is another layer of immune protection, but the quality of MBC responses in naive and coronavirus disease 2019 (COVID-19)-recovered individuals after vaccination remains ill defined. We studied longitudinal cohorts of naive and disease-recovered individuals for up to 2 months after SARS-CoV-2 mRNA vaccination. We assessed the quality of the memory response by analysis of antibody repertoires, affinity, and neutralization against variants of concern (VOCs) using unbiased cultures of 2,452 MBCs...
09 / 14 / 2021
A subset of Kupffer cells regulates metabolism through the expression of CD36
Camille Blériot, Emelie Barreby, Garett Dunsmore, Raphaelle Ballaire,..., Nicolas Venteclef, Matteo Iannacone, Myriam Aouadi, Florent Ginhoux
Tissue macrophages are immune cells whose phenotypes and functions are dictated by origin and niches. However, tissues are complex environments, and macrophage heterogeneity within the same organ has been overlooked so far. Here, we used high-dimensional approaches to characterize macrophage populations in the murine liver. We identified two distinct populations among embryonically derived Kupffer cells (KCs) sharing a core signature while differentially expressing numerous genes and proteins: a major CD206loESAM- population (KC1) and a minor CD206hiESAM+ population (KC2)...
09 / 07 / 2021
Allosteric inhibition of HER2 by Moesin-mimicking compounds targets HER2-positive cancers and brain metastases
Camille Faure, Rym Djerbi-Bouillié, Anaïs Domingot, Haniaa Bouzinba-Segard, Saïd Taouji,..., Jean-Luc Lenormand, Eric Chevet, Sandrine Bourdoulous
Therapies targeting the tyrosine kinase receptor HER2 have significantly improved survival of HER2+ cancer patients. However, both de novo and acquired resistance remain a challenge, particularly in the brain metastatic setting. Here we report that, unlike other HER tyrosine kinase receptors, HER2 possesses a binding motif in its cytosolic juxtamembrane region that allows interaction with members of the ezrin/radixin/moesin (ERM) family. Under physiological conditions, this interaction controls the localization of HER2 in ERM-enriched domains and stabilizes HER2 in a catalytically repressed state...
07 / 27 / 2021
Arrest of WNT/β-catenin signaling enables the transition from pluripotent to differentiated germ cells in mouse ovaries
Morgane Le Rolle, Filippo Massa, Pam Siggers, Laurent Turchi, Agnès Loubat, Bon-Kyoung Koo, Hans Clevers, Andy Greenfield, Andreas Schedl, Marie-Christine Chaboissier, Anne-Amandine Chassot