Descripción del proyecto
Predicción del reconocimiento de antígenos por los linfocitos T
Nuestro sistema inmunitario comprende varias subpoblaciones de linfocitos T, cada uno con un perfil y una función particulares. Existe un gran interés por el reconocimiento de microorganismos patógenos y antígenos del cáncer por los linfocitos T para mejorar el diagnóstico de enfermedades. El equipo del proyecto nextDART, financiado por el Consejo Europeo de Investigación, desarrollará una novedosa tecnología basada en las moléculas del complejo principal de histocompatibilidad I. Los investigadores se centrarán en la detección de las especificidades de los linfocitos T en muestras biológicas, y asociarán la especificidad del antígeno con la secuencia de los receptores de los linfocitos T. La tecnología predecirá el reconocimiento y la especificidad de los receptores de linfocitos T para epítopos específicos, lo que ofrecerá un medio para prever el reconocimiento inmunitario por parte de los linfocitos T.
Objetivo
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.
Ámbito científico
- natural sciencesbiological sciencesgeneticsDNA
- medical and health sciencesclinical medicineoncologylung cancer
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesbasic medicineimmunologyimmunotherapy
- medical and health sciencesmedical biotechnologycells technologies
Programa(s)
Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
2800 Kongens Lyngby
Dinamarca