Our interest is the study of the molecular bases that underlie the immune response and to decipher the molecular mechanisms that participate in the formation of the immune synapse and in the biological responses that derive from it. The synapse is a zone of close contact, which forms an interface between cells of the immune system, which acts as a dynamic and plastic platform for intracellular signaling, and which integrates in space and time the spatial, mechanical and biochemical signals that are involved in the immune response, both cellular and humoral responses. We study the intracellular traffic involved in the polarized secretion of exosomes at the synapse. Exosomes are lipid double membrane nanovesicles (50-100 nm) that accumulate as intraluminal vesicles within late endosomes to form multivesicular bodies (MVBs). Cellular stimulation induces the fusion of MVBs with the plasma membrane and the secretion of intraluminal vesicles as exosomes. In the immune system, activation of the T-lymphocyte antigen receptor (TCR) induces the acquisition of key effector and immunoregulatory functions involving exosomes. These functions are the cytolytic activity of cytotoxic T lymphocytes (CTLs) and activation-induced apoptosis (AICD) of T lymphocytes. In CTLs, MVBs are called lytic granules. When the TCR is activated, the CTLs polarize their lytic granules to secrete pro-apoptotic molecules (Fas ligand, perforins, granzymes) at the synapse, which induces apoptosis of target cells, such as tumor cells. Both CTLs and T helper lymphocytes secrete exosomes with pro-apoptotic molecules, such as the Fas ligand (FasL), and this is involved in activation-induced cell death (AICD). AICD mediated by the Fas / FasL system is considered key in the control of T lymphocyte homeostasis and defects in AICD lead to autoimmune diseases. The specific objectives are: 1) To study the mechanisms that control the polarized trafficking of MVBs / lytic granules in T lymphocytes and study the participation of MVBs in exosome secretion. 2) To study the involvement of exosomes in apoptosis induced by CTLs, as well as in the AICD process.

Trabajo presentado en la Asamblea General Nanomed CSIC, celebrada en Madrid (España) el 21 de marzo de 2022.

Peer reviewed