Francisco Sánchez-Madrid- Intercellular Communication in the Immune System

Activation of the adaptive immune response requires the stimulation of T lymphocytes by antigen-presenting cells (e.g. dendritic cells, DC) through intimate contacts. These contacts (“immune synapses”) are hubs that transmit information from the DC to the T cell, but  information also travels in reverse, from the T cell to the DC. This reverse transmission depends on receptor-dependent adhesive contacts, soluble factors (e.g. cytokines/chemokines) and vesicles (e.g. exosomes). Exosomes are small extracellular vesicles formed at multivesicular bodies (MVB) and released towards the DC through MVB fusion with the plasma membrane. Exosomal content is sorted through precise mechanisms and differs from the global cell cytosolic content. We aim to determine the specific chaperone activity at the T cell centrosome upon activation that forms part of an extended interactome that can influence the composition of exosomes in T cells. This interactome (folding, stabilization and terminal degradation) will therefore influence the T cell-DC dialogue during immune synapse. Our research aims to  decipher the role of specific bits of information originated within the T cell and carried in exosomes that depend on the centrosomal-interactome activity to analyze the resulting dendritic cell ability to fight against infections. These studies will open avenues for new vaccination strategies.