Project Details
Projekt
Tracking T cell receptor-dependent imprinting of cellular differentiation states during polyclonal and chronic immune responses (B09)
Subject Area
Immunology
Term
from 2013 to 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 210592381
While natural T cell populations are thought to consist of a broad and continuous spectrum of TCR affinities and T cell differentiation states, direct investigation of affinity-dependent T cell differentiation within polyclonal TCR repertoires has so far not been experimentally feasible. We have recently developed novel tools which allow for the first time to track defined polyclonal TCR repertoires with single-TCR resolution throughout the entire course of an immune response. Furthermore, we could experimentally demonstrate that the antigen-specific TCR repertoire from naïve precursor populations indeed entails a very wide range of affinities, and we have built up defined polyclonal TCR repertoires which are representative of physiological polyclonality. In this project, we want to use these tools to decipher how TCR affinity shapes CD8+ T cell fate within polyclonal repertoires during infection and tumor disease. In particular, we aim at dissecting the dynamic interplay of structural TCR affinity and phenotypic plasticity during chronic or repetitive antigen exposure.
DFG Programme
Collaborative Research Centres
Applicant Institution
Ludwig-Maximilians-Universität München
Project Heads
Privatdozent Dr. Veit Buchholz, from 1/2017 until 12/2020; Professor Dr. Dirk Busch; Professor Dr. Kilian Schober, since 1/2021
