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Decoding at systems-level the crosstalk between the T cell antigen receptor, the CD28 costimulator and the PD-1 coinhibitor under physiological and pathological conditions.

Total Cost €


EC-Contrib. €






 BASILIC project word cloud

Explore the words cloud of the BASILIC project. It provides you a very rough idea of what is the project "BASILIC" about.

computational    inflammatory    situation    experimental    pathogenic    pay    architecture    levels    ing    methodology    scales    hub    understand    capacity    central    places    ox40    positive    coinhibitors    tuned    tnfr    autistic    severe    encounters    harmful    negative    signals    crosstalk    clonal    lack    expansion    convey    proteomics    decode    informations    tumoral    malfunctions    stems    think    comprehension    coinhibitory    combining    genetic    epigenomics    fundamental    multidisciplinary    costimulatory    cell    addicted    decisions    place    physiology    sole    superfamily    favorable    triggers    satisfying    creates    occupies    presenting    largely    cd28    ignored    plays    organismal    antigen    stoichiometry    signalosomes    functions    costimulator    receptors    unveil    costimulators    informed    integrate    although    ideal    receptor    anti    nature    molecular    probe    disrupt    straddling    multiple    isolation    superseded    immunopathologies    signaling    inputs    cells    cooperate    primary    tcr    coinhibitor    optimal    dynamics    lat    novelty    pd   

Project "BASILIC" data sheet

The following table provides information about the project.


Organization address
address: RUE MICHEL ANGE 3
city: PARIS
postcode: 75794

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country France [FR]
 Total cost 2˙000˙000 €
 EC max contribution 2˙000˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-ADG
 Funding Scheme ERC-ADG
 Starting year 2018
 Duration (year-month-day) from 2018-08-01   to  2022-07-31


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 


 Project objective

Although the T cell antigen receptor (TCR) occupies a central place in T cell physiology, it does not work in isolation and the signals it triggers are tuned by receptors that convey positive (costimulators) and negative (coinhibitors) informations. We lack a satisfying comprehension of the way T cells integrate such multiple inputs to make informed decisions. The proteomics-based methodology we developed around the TCR places us in a favorable situation to decode at systems-level the crosstalk between the TCR, the CD28 costimulator and the PD-1 coinhibitor signaling pathways. The novelty of our approach stems from (1) its use of primary T cells, (2) its capacity to probe the architecture and dynamics of signalosomes resulting from T cell-antigen presenting cell encounters, (3) the attention we pay to the stoichiometry of the studied signalosomes, a key parameter largely ignored in previous studies, and (4) its multidisciplinary nature straddling molecular and organismal scales. Our specific aims are: Aim 1. To understand how the TCR and CD28 signaling pathways cooperate to achieve optimal T cell responses. Aim 2. To determine whether CD28 is the sole target of the PD-1 coinhibitor. Aim 3. To determine how under inflammatory conditions CD28 functions can be superseded by those of OX40, a costimulator of the TNFR superfamily. Aim 4. To unveil how malfunctions of LAT, a key signaling hub used by the TCR, disrupt the TCR-CD28 crosstalk and result in unique pathogenic T cells that by becoming ‘autistic’ to TCR signals and addicted to CD28 signals lead to severe immunopathologies. We think that combining genetic, epigenomics, proteomics, and computational approaches creates ideal experimental conditions to understand at system-levels how TCR, costimulatory, coinhibitory and inflammatory signals are integrated during T cell clonal expansion. Although of fundamental nature, our project should help understanding the harmful role PD-1 plays during anti-tumoral responses.


year authors and title journal last update
List of publications.
2019 Guillaume Voisinne, Kristof Kersse, Karima Chaoui, Liaoxun Lu, Julie Chaix, Lichen Zhang, Marisa Goncalves Menoita, Laura Girard, Youcef Ounoughene, Hui Wang, Odile Burlet-Schiltz, Hervé Luche, Frédéric Fiore, Marie Malissen, Anne Gonzalez de Peredo, Yinming Liang, Romain Roncagalli, Bernard Malissen
Quantitative interactomics in primary T cells unveils TCR signal diversification extent and dynamics
published pages: 1530-1541, ISSN: 1529-2908, DOI: 10.1038/s41590-019-0489-8
Nature Immunology 20/11 2020-04-24
2019 Javier Celis-Gutierrez, Peter Blattmann, Yunhao Zhai, Nicolas Jarmuzynski, Kilian Ruminski, Claude Grégoire, Youcef Ounoughene, Frédéric Fiore, Ruedi Aebersold, Romain Roncagalli, Matthias Gstaiger, Bernard Malissen
Quantitative Interactomics in Primary T Cells Provides a Rationale for Concomitant PD-1 and BTLA Coinhibitor Blockade in Cancer Immunotherapy
published pages: 3315-3330.e7, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2019.05.041
Cell Reports 27/11 2019-09-05

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