Endocytic network of human dendritic cell upon T cell recognition
T cell mitochondria (orange) shaped by cytoskeleton (green) next to nucleus (blue).
Reorganization and Remodelling
of immune cells
to communicate an effective immune response
During an infection immune cells have a short period of time to orchestrate an adequate immune response. On top of that, research has shown that immune cells spend only a short time in each others vicinity. To ensure rapid and efficient communication, antigen-presenting cells and T cells have developed a unique cell-cell interface that supports rapid and efficient delivery of messages upon cell-cell interaction.
At ECResearchlab we use multifarious state-of-the-art microscopy techniques to study the molecular mechanisms behind effective cell-cell communication and found that cognate immune cell-cell interaction drives remodelling and reorganisation of:
(1) the late and recycling endocytic compartment to effectively initiate anti-viral responses
(2) the nanoscaled organization of T cell receptors at the cell-cell interface to enable effective T cell activation
(3) mitochondrial localization, shape and function, determining the amplitude of a T cell's response.
(4) the plasmamembrane lipid content and ESCRT protein composition at the cell-cell interface to generate a protective (high affinity) antibody response.
Currently, we are targeting the various molecular mechanisms responsible for this T cell remodelling with the aim to be able to shape the response of
(a) regulatory T cell during transplantation, and
(b) boost helper T cells during vaccination of elderly.
Ageing of the immune system is characterised by a progressive deterioration of the endocytic compartment in immune cells which is accompanied by a loss of immunity. However, the mechanism underlying this causal relationship is still elusive. Early research results indicate that T cells from elderly are less efficiently able to adapt and remodel upon cognate interaction. Future work will focus on elucidating changes in T cell's cytoskeletal and endocytic compartment that are responsible for age-related immunodeficiency.