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.