THE PHARMACOLOGY OF THE T-CELL RECEPTOR A ND ITS LIGANDS

The trimolecular system made of the T cell receptor (TCR), the antigen ic peptide and the major histocompatibility complex (MHC) glycoprotein plays a pivotal role in the interaction between target cells and effe ctor cells of the immune system. Based on the knowledge of MHC-peptide and MHC-peptide-TCR interactions, the pharmacological principles of T CR-ligand interaction have recently been defined. It is now well estab lished that TCR ligands may be endowed with agonist, partial agonist o r antagonist properties. The design of pharmacologically active TCR li gands that modulate recognition of target cells by T lymphocytes and t heir use in new immunotherapeutic approaches or autoimmune diseases re present one of the major scientific and clinical challenges of the nex t decade. Further, the pharmacological principles of TCR-ligand intera ction should allow a better understanding of the mecanisms involved in T cell onto-genesis and in evasion to the immune system.