Antigen Presentation in Dendritic Cells

Sebastian AMIGORENA - credit Thibaut Voisin 1 copie copie

Sebastian Amigorena Team Leader Tel:

Adaptive immune responses are initiated by the clonal selection of naive T lymphocytes, which recognize their cognate ligands through antigen-specific T cell receptors. T cell receptors are specific for MHC/peptides complexes. These peptides are generated from internalized antigens that are degraded in endocytic compartments. The peptides are then loaded on MHC molecules and the complexes are transported to the cell surface. Clonal selection also requires the physical encounter of dendritic cells and T lymphocytes, an event that occurs in the T cell zones of lymph nodes. Naïve T cells then expand and differentiate into effector T lymphocytes that acquire either cytotoxic activity or secrete high amounts of certain cytokines. Some of these T cells become “effectos” (the ones that have direct roles in the immune response, including helper functions for CD4+ T cells, and cytotoxic functions for CD8+ T cells), while other T cells differentiate into resting memory cells. The latter are longed lived and can be reactivated upon re-infection with the same microbe, initiating a more rapide and effective recall response.

Figure 1 : Phagosomal degradation of OVA is dependent on phagosome maturation kinetics. (A) Latex beads conjugated to OVA were internalized by bone marrow-derived dendritic cells (DC) and macrophages (MO) and analyzed by confocal microscopy after labeling of OVA (blue), LAMP-1 (red) and F-actin (green). Shown are maximum projections of 5 focal planes with a step width of 0.3 μm. Bar: 10 μm.
Figure 1 : Phagosomal degradation of OVA is dependent on phagosome maturation kinetics. (A) Latex beads conjugated to OVA were internalized by bone marrow-derived dendritic cells
(DC) and macrophages (MO) and analyzed by confocal microscopy after labeling of OVA (blue), LAMP-1 (red) and F-actin (green). Shown are maximum projections of 5 focal planes with a step width
of 0.3 μm. Bar: 10 μm.

Our team is interested in the molecular analysis of immune responses, particularly in the context of cancer. Our main objectives are:

  • To understand the molecular basis of antigen presentation in dendritic cells. We analyse the intracellular membrane transport pathways involved and attempt to identify the intracellular compartments where peptide-MHC complexes form. We also investigate the ability and involvement of different mouse and human DC population in immune responses against tumors.
  • To analyse the molecular determinants that control gene expression during T cell differentiation and the generation of immunological memory. We attempt to understand how the organisation of chromatin determines the epigenetic control of T cell responses in vitro and in vivo.
Figure 2: Using bone marrow chimeric mice, adoptively transferred tumors expressing different fluorescent proteins and in vivo infusion of propidium iodide, we can follow dynamically anti tumor T cells (here in light blue; false color) dead tumor cells (in red) and collagen fibers (blue, second harmonics).
Figure 2: Using bone marrow chimeric mice, adoptively transferred tumors expressing different fluorescent proteins and in vivo infusion of propidium iodide, we can follow dynamically anti tumor T cells (here in light blue; false color) dead tumor cells (in red) and collagen fibers (blue, second harmonics).

Our technological expertise ranges from the most fundamental approaches to study membrane transport in lymphocytes and dendritic cells (subcellular compartmentalization, intravital microscopy, phagosomal functions), the systematic analysis of gene expression and it regulation (RNAseq, Chip Seq, proteomics) and physiological and pathological immune responses (mouse models for cancer immunity, immunomodulation/vaccination, human clinical studies in cancer).

Key publications

Year of publication 2018

Paul Gueguen, Luigia Pace, Christel Goudot, Elina Zueva, Nina Burgdorf, Joshua J. Waterfall, Jean-Pierre Quivy, Geneviève Almouzni, Sebastian Amigorena (2018 Jan 12)

The epigenetic control of stemness in CD8+ T cell fate commitment

Science : 359 : 177-186 : DOI : 10.1126/science.aah6499

Year of publication 2017

Christel Goudot, Alice Coillard, Alexandra-Chloé Villani, Paul Gueguen, Adeline Cros, Siranush Sarkizova, Tsing-Lee Tang-Huau, Mylène Bohec, Sylvain Baulande, Nir Hacohen, Sebastian Amigorena, Elodie Segura (2017 Sep 21)

Aryl Hydrocarbon Receptor Controls Monocyte Differentiation into Dendritic Cells versus Macrophages.

Immunity : 582-596.e6 : DOI : S1074-7613(17)30374-6
Andrés Alloatti, Derek C Rookhuizen, Leonel Joannas, Jean-Marie Carpier, Salvador Iborra, Joao G Magalhaes, Nader Yatim, Patrycja Kozik, David Sancho, Matthew L Albert, Sebastian Amigorena (2017 Jul 1)

Critical role for Sec22b-dependent antigen cross-presentation in antitumor immunity.

The Journal of experimental medicine : 2231-2241 : DOI : 10.1084/jem.20170229

Year of publication 2016

Christine Sedlik, Adèle Heitzmann, Sophie Viel, Rafik Ait Sarkouh, Cornélie Batisse, Frédéric Schmidt, Philippe De La Rochere, Nathalie Amzallag, Eduardo Osinaga, Pablo Oppezzo, Otto Pritsch, Xavier Sastre-Garau, Pascale Hubert, Sebastian Amigorena, Eliane Piaggio (2016 Sep 14)

Effective antitumor therapy based on a novel antibody-drug conjugate targeting the Tn carbohydrate antigen.

Oncoimmunology : e1171434 : DOI : 10.1080/2162402X.2016.1171434

Year of publication 2015

Alloatti A1, Kotsias F2, Pauwels AM3, Carpier JM, Jouve M, Timmerman E, Pace L, Vargas P, Maurin M, Gehrmann U, Joannas L, Vivar OI, Lennon-Duménil AM, Savina A, Gevaert K, Beyaert R, Hoffmann E, Amigorena S. (2015 Dec 15)

Toll-like Receptor 4 Engagement on Dendritic Cells Restrains Phago-Lysosome Fusion and Promotes Cross-Presentation of Antigens.

Immunity : DOI : 10.1016/j.immuni.2015.11.006

Year of publication 2012

Luigia Pace, Andy Tempez, Catharina Arnold-Schrauf, Fabrice Lemaitre, Philippe Bousso, Luc Fetler, Tim Sparwasser, Sebastian Amigorena (2012 Nov 1)

Regulatory T cells increase the avidity of primary CD8+ T cell responses and promote memory.

Science (New York, N.Y.) : 532-6 : DOI : 10.1126/science.1227049
All publications