In this lecture, the quantitative and qualitative aspects of peptide antigen recognition by the T receptor for antigen were presented. Recent work has shown that a single peptide-histocompatibility molecule (MHC) complex is necessary and sufficient to induce CD4 T cell activation. The digital nature of the response (+ or -) has been demonstrated. The role of association constants (receptor detachment for the ag/MHC complex) and interaction time (which is interrupted and cumulative) was highlighted. These results have led to the proposal of an activation model that associates a series of membrane events, including the clustering of antigen receptors. Numerous costimulatory molecules whose ligands are present on the surface of dendritic cells amplify and modulate the signaling pathways that induce T cell effector functions. Numerous intracellular signaling pathways are thus involved, and the modalities of signal integration, their dynamics and their localization at the synapse between antigen-presenting cells and T lymphocytes are the subject of much research. Nevertheless, an anatomical and dynamic compartmentalization of this synapse has been described, which accounts for cell activation.
One of the important consequences of lymphocyte activation is the rapid adaptation of lymphocyte metabolism, enabling these cells to increase in volume and divide rapidly (every 6 to 8 hours), which involves active synthesis of membranes, i.e. phospholipids, as well as proteins and nucleic acids (RNA and DNA). These adaptations are controlled by two key proteins, cMyc and mTORC, which induce ad hoc metabolic modifications (notably the use of glucose and glutamine as energy sources). We can now define the "metabolic profile" of the various effector, regulatory or memory T cell entities, which accounts for their response capacity.
The lecture was followed by a seminar entitled "Towards an integrative biology of T lymphocytes", given by Bernard Malissen, researcher at the Marseille Luminy Immunology Center. B. Malissen described an innovative approach to the refined analysis of the multiple protein-protein interactions involved in T-cell activation, based on the construction of transgenic mouse lines in which each key activation protein is linked to a "tag" that isolates the proteins with which each of them interacts. This global - systemic - approach makes it possible to perceive the complexity of the signaling pathways involved, and to envisage a quantitative approach to these phenomena.
