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Antigen Presentation by Dendritic Cells to T cells (APreT)

Team Saveanu / Guermonprez

Department Nephrology, Immunology and Hematology







Antigen Presentation by Dendritic Cells to T cells

Dendritic cells (DCs) are the sentinel cells of the immune system. DCs present antigen to T lymphocytes and regulate their activation. T lymphocytes recognize and eliminate infected or cancer cells. Therefore, understanding the biology of T cell activation by DCs is crucial for the development of vaccines and immunotherapies. Also, inappropriate regulation of T lymphocyte activation by DCs supports the development of chronic inflammatory diseases and auto-immunity.

Our team investigates the mechanisms underpinning T cell activation by DCs. We implement multi-scale and multi-disciplinary approaches to tackle 3 research topics.

1- Ontogeny and dynamics of DC populations.

At homeostasis, DCs populations are continuously renewed from bone marrow hematopoietic stem cells. The dynamics of DCs population impacts on immune responses. We aim at understanding: i) the ontogenetic processes enabling the production of various DCs subsets (classical and inflammatory) and its regulation during cancer; ii) how DCs traffic to solid tumours. This project implements contemporary technologies such as high dimensional profiling, single cell RNAseq as well as humanised mice models. Building on a better understanding of DC populations, we design and evaluate therapeutic interventions aiming at increasing DC infiltration in solid tumours to stimulate anti-tumour immunity.

2- Antigen cross-presentation/presentation by MHCI/II.

In most instances, induction of antigen-specific T cell responses relies on the phagocytosis of particulate antigens by DCs. This is highly relevant for tumour antigens that are engulfed together with cancer cell debris. The dynamics of antigen-containing phagosomes is controlled by their interactions with multiple types of endosomes (early, storage, late, lysosomes). These interactions ultimately control the formation and presentation of antigenic peptides-MHC I and II complexes. We investigate if and how phagosome-associated proteins control phagosome dynamics and antigen presentation by MHCI/II to T lymphocytes in DCs subsets. Both, unbiased genetic screen using CRISPR-Cas9 and hypothesis driven approaches (Rab GTPases and PI3Kinases) are developed in the lab to tackle the molecular cell biology of antigen presentation by DCs.

3- T lymphocyte activation, fate and function.

The recognition of MHC-peptide complex by the T cell receptor leads to the formation of the immune synapse. We aim at understanding how intracellular trafficking in T lymphocytes supports the recognition of MHC-peptides complexes by the T cell receptor. Using intracellular live imaging, advanced microscopy techniques (FRET) and cutting-edge proteomics (in vivo biotynilation via APEX2), we investigate the endocytic mechanisms controlling TCR signalling at the DC-T cell synapse. Specifically, we are addressing how the balance between recycling or degradation of several key proteins for T cell activation such as TCRzeta, Lck and LAT controls signalling downstream TCR triggering.

In addition, we investigate the long-term consequences of antigen presentation by DCs subsets on the differentiation, fate and function of T lymphocytes. DCs are composed of multiple subsets which are also regulated by context-dependent signals. We are investigating how cell-intrinsic DCs features and environmental cues (including factors from the tumour micro-environment) shape the diversity of antigen-presenting DCs and anti-tumour T cell responses. In particular, we investigate how DCs imprint some trafficking behaviour in T cells and impact on T cell fate in the context of breast and lung cancer.


Landmark publications

  • Publication date : 01 April 2022 More

    The role of endocytic trafficking in antigen T cell receptor activation
    Biomed J.

    Autors : Evnouchidou Irini Caillens Vivien Koumantou Despoina Saveanu Loredana

  • Publication date : 15 March 2021 More

    Harnessing Mesenchymal Stromal Cells for the Engineering of Human Hematopoietic Niches
    Front Immunol.

    Autors : Alice Pievani Roberto Savoldelli Juliane Poelchen Elisa Mattioli Giorgio Anselmi Girardot Alice Jochen Utikal Bourdely Pierre Marta Serafini Guermonprez Pierre

  • Publication date : 20 October 2020 More

    The Role of Insulin Regulated Aminopeptidase in Endocytic Trafficking and Receptor Signaling in Immune Cells
    Front Mol Biosci.

    Autors : Delphyne Descamps Evnouchidou Irini Caillens Vivien Carole Drajac Sabine Riffault Peter van Endert Saveanu Loredana

  • Publication date : 18 August 2020 More

    Transcriptional and Functional Analysis of CD1c+ Human Dendritic Cells Identifies a CD163+ Subset Priming CD8+CD103+ T Cells

    Autors : Bourdely Pierre Anselmi G Vaivode K Ramos RN Missolo-Koussou Y Hidalgo S Tosselo J Nuñez N Richer W Vincent-Salomon A Saxena A Wood K Lladser A Piaggio E Helft J Guermonprez Pierre

  • Publication date : 02 June 2020 More

    IRAP-dependent endosomal T cell receptor signalling is essential for T cell responses
    Nat Commun.

    Autors : Evnouchidou Irini Pascal Chappert Benadda Samira Andres Zucchetti Mirjana Weimershaus Bens Marcelle Caillens Vivien Koumantou Despoina Lotersztajn Sophie Peter van Endert Jean Davoust Guermonprez Pierre Claire Hivroz David A Gross Saveanu Loredana

  • Publication date : 28 April 2020 More

    Engineered niches support the development of human dendritic cells in humanized mice
    Nat Commun.

    Autors : Giorgio Anselmi Kristine Vaivode Charles-Antoine Dutertre Bourdely Pierre Yoann Missolo-Koussou Evan Newell Oliver Hickman Kristie Wood Alka Saxena Julie Helft Florent Ginhoux Guermonprez Pierre

  • Publication date : 01 October 2019 More

    Origin and development of classical dendritic cells.
    Int Rev Cell Mol Biol.

    Autors : Guermonprez Pierre Yohan Gerber Kristine Vaivode Pierre Bourdely Julie Helft

  • Publication date : 02 September 2019 More

    Is there a place and role for endocytic TCR signaling?
    Immunol Rev.

    Autors : Saveanu Loredana Zucchetti AE Evnouchidou Irini Ardouin L Hivroz C

  • Publication date : 20 March 2017 More

    IRAP+ endosomes restrict TLR9 activation and signaling
    Nat Immunol.

    Autors : Babdor J Descamps D Adiko AC Tohmé M Maschalidi S Evnouchidou Irini Vasconcellos LR De Luca M Mauvais FX Garfa-Traore M Brinkmann MM Chignard M Manoury B Saveanu Loredana

  • Publication date : 20 December 2016 More

    The Heterogeneity of Ly6Chi Monocytes Controls Their Differentiation into iNOS+ Macrophages or Monocyte-Derived Dendritic Cells

    Autors : Menezes S Melandri D Anselmi G Perchet T Loschko J Dubrot J Patel R Gautier EL Hugues S Longhi MP Henry JY Quezada SA Lauvau G Lennon-Duménil AM Gutiérrez-Martínez E Bessis A Gomez-Perdiguero E Jacome-Galarza CE Garner H Geissmann F Golub R Nussenzweig MC Guermonprez Pierre


Site de référence pour les Appels à Projets

Les dernières publications marquantes

  • Publication date : 17 January 2023 More

    ROCK2 interacts with p22phox to phosphorylate p47phox and to control NADPH oxidase activation in human monocytes

    Autors : Asma Tlili Pintard Coralie Hurtado-Nedelec Maria Margarita Liu Dan Viviana Marzaioli Thieblemont Nathalie Dang Pham My-Chan El Benna Jamel

  • Publication date : 30 November 2022 More

    Comparative Analysis of a Locally Resampling MR Elastography Reconstruction Algorithm in Liver Fibrosis

    Autors : Page Gwenael JULEA Felicia Paradis Valérie Vilgrain Valérie Valla Dominique Van Beers Bernard Garteiser Philippe

  • Publication date : 03 November 2022 More

    JAK2V617F mutation drives vascular resident macrophages toward a pathogenic phenotype and promotes dissecting aortic aneurysm
    Nature Communications.

    Autors : Rida Al-Rifai Marie Vandestienne Jean-Rémi Lavillegrand Tristan Mirault Julie Cornebise Poisson Johanne Ludivine Laurans Bruno Esposito Chloé James Olivier Mansier Pierre Hirsch Fabrizia Favale Rayan Braik Camille Knosp Jose Vilar Giuseppe Rizzo Alma Zernecke Antoine-Emmanuel Saliba Alain Tedgui Maxime Lacroix Lionel Arrive Ziad Mallat Soraya Taleb Marc Diedisheim Clément Cochain Rautou Pierre-Emmanuel Hafid Ait-Oufella