Dissecting mechanisms of trogocytosis and their role in regulating T cell responses

• Applicant: Dr. Jan Rohr
• Subject Area: Immunology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 459834048

Based on their ability to eliminate infected or malignant cells CD8+ T lymphocytes take centre stage in combating many infectious diseases and cancers. Their activity depends on signals provided by professional antigen-presenting cells. However, there is mounting evidence that CD8+ T lymphocytes are not solely subordinate executioners of orders provided by other cell types, but that they themselves actively regulate their own population dynamics and differentiation - akin to bacterial quorum-regulation. Currently we are only beginning to unravel the full scope of biological mechanisms contributing to quorum-regulation among T lymphocytes. An aspect that has received little scientific attention in this regard is collective regulation of the maintenance and degradation of immune-regulatory proteins. Mechanistically, this may be accomplished by trogocytosis, whose precise mode of action and functional implications are, however, not well understood. To unravel these aspects, we have developed several novel experimental systems, which enable the examination of this process with high sensitivity. We will use these to investigate 1.) the molecular mechanism underlying the transcellular protein transfer, 2.) the mechanisms regulating the fate of trogocytosed molecules, 3.) the impact of receptor-ligand affinity on the efficiency of trogocytosis, 4.) the functionality of trogocytosed molecules re-appearing at the cell membrane and 5.) whether tumour cells can actively evade trogocytosis ? Answering these seminal questions will not only reveal fundamental aspects of immune regulation, but also provide new targets for therapeutic interventions.

• DFG Programme: Research Grants