Abstract

How T cell activation is regulated on the molecular level at the immune synapse remains of central interest to immunology. This process involves complex dynamic interactions between cell-surface receptors, adhesion molecules, signal transduction elements, and cytoskeletal proteins, but remains incompletely understood.

Intracellular vesicular compartments are involved in removing spent receptors from the immune synapse, as well as directing specialized cargo to the synapse for release towards target cells. Whether intracellular vesicles are also involved in the activating processes at the immune synapse during T cell signalling remains unknown.

We here describe membrane-proximal endosomal vesicles which are intimately involved with the architecture of the immune synapse. These sub-synaptic vesicles can interact with surface microclusters of signalling proteins during T cell activation, and in doing so, boost the signalling capacity of individual microclusters. Thus docking of sub-synaptic vesicles to microclusters at the plasma membrane through an intracellular adhesion event may complete signal¬ling complexes during T cell activation.