Introduction

Autoimmune diseases are, by definition, ones in which pathology results directly or indirectly from specific immune recognition of self-tissues. Although the ultimate mediators of destruction may include T cells, antibody and complement or activated macrophages, attention has focused on the central interaction of antigenic peptide, major histocompatibility complex (MHC) molecule and T cell receptor (TCR) needed to trigger recognition. The paradigm for analysis of these events has come largely from studies in a small number of mouse and rat models. In particular, experimental allergic encephalomyelitis (EAE), an experimentally induced disease where animals show CNS inflammation sometimes including demyelination, is a model for some aspects of multiple sclerosis (MS), while the non-obese diabetic (NOD) mouse offers a good model for the spontaneous, autoimmune destruction of pancreatic beta cells in insulin dependent, type I diabetes (IDDM).

Experiments in such models have raised the hope that characterization of the molecular components involved in the activation of autoreactive T cells will pave the way for the design of highly selective immunosuppressive therapies. Since the stimulation of specific T cells to kill targets or secrete cytokines depends on signals which follow precise binding of the TCR to a complex formed by antigenic peptide lodged in the ‘cleft’ of a specific MHC molecule, therapeutic intervention may be offered by competition with, or blocking of, any of these compounds. Indeed, many major pharmaceutical companies currently base much of their research and development for diseases such as rheumatoid arthritis and diabetes on this premise.