DIFFERENTIAL SIGNALING BY LYMPHOCYTE ANTIGEN RECEPTORS

Studies performed during the past several years make plain that ligand occupancy of antigen receptors need not necessarily provoke identical responses in all instances. For example, ligation of antigen receptor s may stimulate a proliferative response, induce a state of unresponsi veness to subsequent stimulation (anergy), or induce apoptosis. How do es a single type of transmembrane receptor induce these very heterogen eous cellular responses? In the following pages, we outline evidence s upporting the view that the nature of the ligand/receptor interaction directs the physical recruitment of signaling pathways differentially inside the lymphocyte and hence defines the nature of the subsequent i mmune response. We begin by providing a functional categorization of a ntigen receptor components, considering the ways in which these compon ents interact with the known set of signal transduction pathways, and then review the evidence suggesting that differential signaling throug h the TCR is achieved by qualitative differences in the effector pathw ays recruited by TCR, perhaps reflecting the time required to bring co mplicated signal transduction elements into proximity within the cell. The time-constant of the interaction between antigen and receptor in this way determines, at least in part, the nature of the resulting res ponse. Finally, although our review focuses substantially on T cell re ceptor signaling, we have included a less detailed description of B ce ll receptor signaling as well, simply to emphasize the parallels that exist in these two closely related systems.