Our research focuses on understanding the molecular mechanisms governing T and B lymphocyte activation. We investigate how αβ and γδ T lymphocytes transmit ligand-binding information across the plasma membrane through their antigen receptors and the signaling pathways that regulate their activation. Additionally, we explore the nano-organization of the B-cell antigen receptor and how defective B-cell activation contributes to immunopathologies. Bridging fundamental immunology with translational medicine, we focus on T cell-based cancer immunotherapy. Our work aims to harness CD3 diversity and refine synthetic chimeric antigen receptor (CAR) design to enhance CAR T-cell therapy. We also explore how the tumor microenvironment influences T-cell motility and how γδ T cells can be leveraged to optimize tumor immunotherapy. By uncovering key principles of lymphocyte signaling, we strive to advance cancer immunotherapy, autoimmune disease research, and immunodeficiency treatment, paving the way for next-generation immunotherapies.