Chapter 21. The T Cell – Antigen Presenting Cell Interaction as a Site for Immunosuppressive Interventions

Abstract

Publisher Summary The T cell–antigen presenting cell (APC) interaction provides a large number of molecular targets for immunosuppressive pharmacological intervention. The activation of T lymphocytes, by antigen displayed on the surface of specialized cells, termed APC, is the initial step of all immune responses. The activation step involves a series of molecular interactions between T cell and APC. Antibody inhibition data suggest that interrupting any of the molecular interactions, between these two cells, can potentially result in immunosuppression. This chapter discusses the possible approaches aimed at interfering with the T cell–APC interaction. The primary therapeutic targets of immunosuppression are autoimmune diseases (AID) and transplantation. Immunosuppression, however, is beneficial as long as it is targeted to a pathological response, but potentially dangerous if it compromises host defense against pathogens. Proteins, such as monoclonal antibodies (mAbs) that bind to the antigen receptor of T cells (TCR) and prevent its interaction with APC, can interfere with T cell activation. The mAbs, depending on their specificity, can be pan-TCR reactive, chain-specific, recognizing all or most α or β chains, V region-specific, or clonotypic, specific for a particular V α V β combination. Many of these antibodies are available. Such molecules that are directly involved in antigen recognition— that is, TCR and major histocompatibility complex (MHC) molecules —have the greatest potential as targets for immunosuppression because of their high selectivity.