New insights into mechanisms of allograft rejection.

Understanding of the molecular basis of organ allograft rejection has increased tremendously in the past decade. Insight into the nature of the alloantigen and the mechanisms underlying T cell recognition, activation, and differentiation provide novel targets for immunotherapy. Appreciation of the role that peptides present in the human leukocyte antigen groove play in allorecognition provides a new target for synthetic peptide therapy. Elucidation of signal transduction pathways downstream from the T-cell receptor helps to explain the mechanism of action of immunosuppressive agents and impacts the design of new drugs. An understanding of the role of costimulatory molecules, such as CD28, has given rise to new therapies, such as CTLA4-Ig. Information about the mechanisms of cytotoxicity, chemoattraction, and vascular biology similarly has provided new targets for rational drug design. This article highlights new insights into the mechanism of allograft rejection relevant to the design of new immunotherapies.