Descrizione del progetto
Previsione del riconoscimento dell’antigene da parte delle cellule T
Il nostro sistema immunitario comprende diverse sottopopolazioni di cellule T, ciascuna con un profilo e una funzione unici. Esiste un grande interesse per il riconoscimento delle cellule T in relazione agli agenti patogeni e agli antigeni del cancro per migliorare la diagnosi della malattia. Il progetto nextDART, finanziato dal Consiglio europeo della ricerca, svilupperà una nuova tecnologia basata sulle molecole del complesso maggiore di istocompatibilità I. I ricercatori si concentreranno sul rilevamento delle specificità delle cellule T nei campioni biologici e assoceranno la specificità dell’antigene con la sequenza dei recettori delle cellule T. La tecnologia permetterà di prevedere il riconoscimento e la specificità dei recettori delle cellule T per specifici epitopi, offrendo un mezzo per prevedere il riconoscimento immunitario da parte delle cellule T.
Obiettivo
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.
Campo scientifico
- natural sciencesbiological sciencesgeneticsDNA
- medical and health sciencesclinical medicineoncologylung cancer
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesbasic medicineimmunologyimmunotherapy
- medical and health sciencesmedical biotechnologycells technologies
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-STG - Starting GrantIstituzione ospitante
2800 Kongens Lyngby
Danimarca