Basic science for the clinician 30: The immunologic synapse

Interactions between discrete and independent cells, immune or otherwise, present a variety of potential problems. How do you make sure the cells can communicate effectively? How do you preclude neighboring cells from "listening in on a conversation" that may be meant only for one set of "ears"? How can you sharpen the hearing of those ears so they will be capable of detecting small signals but not get distracted by random noise in the system? How can you selectively enhance the sense of hearing in times of great need or urgency and then diminish the "gain" of the system when it is not immediately required? How can you assure that the call will be terminated at the end of the conversation? Passage of communication molecules and/or interaction of cell surface markers require close and stable apposition of the cell delivering the message with the receiving cell. In the nervous system, these problems were successfully addressed in the nerve-nerve or nerve-myocyte (neuromuscular junction) synapses. Not surprisingly, given the parsimony of nature, the immune system uses some of the same design features, even some of the same molecules, to achieve an effective communication strategy. The term "immunologic synapse" was coined only 2 decades ago, but the structure it describes has become a very hot topic in immunology and cell biology. The immunologic synapse allows the activation of a unique T cell, with an antigen receptor recognizing its antigen in the grasp of the antigen-presenting cell's (APC's) major histocompatibility complex (MHC). A better understanding of this transient immune cell-cell interactive structure allows one to weave the functions of T cell antigen receptors, lipid rafts, adaptor molecules, and nuclear signaling molecules together into one cohesive, flowing communication supersystem. Appreciation of the intricacies of the synapse also identifies targets that one day may be used to interfere with antigen-specific immune responses, eg, autoimmunity.