Description du projet
Prévoir la reconnaissance des antigènes par les lymphocytes T
Notre système immunitaire comprend plusieurs sous-populations de lymphocytes T, chacune doté d’un profil et d’une fonction uniques. La reconnaissance des lymphocytes T en relation avec les agents pathogènes et les antigènes cancéreux suscite un grand intérêt dans le cadre de l’amélioration du diagnostic des maladies. Financé par le Conseil européen de la recherche, le projet nextDART développera une nouvelle technologie basée sur les molécules du complexe majeur d’histocompatibilité de classe 1. Les chercheurs se concentreront sur la détection des spécificités des lymphocytes T dans les échantillons biologiques et associeront la spécificité de l’antigène à la séquence des récepteurs des lymphocytes T. Cette technologie permettra de prévoir la reconnaissance et la spécificité des récepteurs des lymphocytes T pour des épitopes spécifiques, proposant ainsi un moyen de prévoir la reconnaissance immunitaire par les lymphocytes T.
Objectif
Our current ability to map T-cell reactivity to certain molecular patterns poorly matches the huge diversity of T-cell recognition in humans. Our immune system holds approximately 107 different T-cell populations patrolling our body to fight intruding pathogens. Current state-of-the-art T-cell detection enables the detection of 45 different T-cell specificities in a given sample. Therefore comprehensive analysis of T-cell recognition against intruding pathogens, auto-immune attacked tissues or cancer is virtually impossible.
To gain insight into immune recognition and allow careful target selection for disease intervention, also on a personalized basis, we need technologies that allow detection of vast numbers of different T-cell specificities with high sensitivity in small biological samples.
I propose here a new technology based on multimerised peptide-major histocompatibility complex I (MHC I) reagents that allow detection of >1000 different T-cell specificities with high sensitivity in small biological samples. I will use this new technology to gain insight into the T-cell recognition of cancer cells and specifically assess the impact of mutation-derived neo-epitopes on T cell-mediated cancer cell recognition.
A major advantage of this new technology relates to the ability of coupling the antigen specificity to the T-cell receptor sequence. This will enable us to retrieve information about T-cell receptor sequences coupled with their molecular recognition pattern, and develop a predictor of binding between T-cell receptors and specific epitopes. It will ultimately enable us to predict immune recognition based on T-cell receptor sequences, and has the potential to truly transform our understanding of T cell immunology.
Advances in our understanding of T cell immunology are leading to massive advances in the treatment of cancer. The technologies I propose to develop and validate will greatly aid this process and have application for all immune related diseases.
Champ scientifique
- natural sciencesbiological sciencesgeneticsDNA
- medical and health sciencesclinical medicineoncologylung cancer
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesbasic medicineimmunologyimmunotherapy
- medical and health sciencesmedical biotechnologycells technologies
Programme(s)
Thème(s)
Régime de financement
ERC-STG - Starting GrantInstitution d’accueil
2800 Kongens Lyngby
Danemark