Monoclonal Antibodies to Adhesion Molecules

Summary

Allograft rejection is accomplished by an immunological cascade involving recognition of alloantigens, activation and proliferation of alloantigen-specific ? cells, target cell lysis mediated by cytotoxic ? cells, and production of cytotoxic antibodies. In each stage of the alloimmune response, cell-cell contacts such as those between ? cells and antigen-presenting cells, ? cells and donor target cells and ? cells and ? cells are necessary. In these cell-cell interactions, adhesion molecules play a pivotal role by participating in cellular adhesion as well as in signal transduction. Alloantigen-specific ? cell activation depends on: (a) interactions between the antigen, the ? cell receptor and molecules of the major histocompatibility complex, and (b) costimulatory signals generated when adhesion molecules bind to their ligands. When major interactions between adhesion molecules and their ligands are blocked, antigen-specific ? cells are selectively induced into a state of anergy. Thus, by using monoclonal antibodies against adhesion molecules, attempts have been made to block the interaction of costimulatory molecules with the objective of inducing donor-specific tolerance.