For much of the last few decades, investigators have concentrated on delineating the parameters that involve the direct activation of the immune system. In general, receptor engagement, by antigen, cytokine, or counterreceptor, initiates a cascade of distinct biochemical events in lymphocytes and other immune cells, leading to downstream effector functions. Concurrent engagement of other (costimulatory) receptors tends to enhance these responses. Inasmuch as these pathways have been described in great detail, strategies to alter immune responses, such as to arrest overactive autoimmune states, to enhance immune responses to tumors or pathogens, or to provoke immunological memory from vaccination have been focused on modulation of these activation processes.
However, recent evidence clearly demonstrates that ligation of another functional class of immune receptors leads instead to inhibition of activation pathways (for review see Parham, P., ed. 1997. NK cells, MHC Class I Antigens, and Missing Self. Immunol. Rev. 155:1–221.). Important information...
