ITAMs versus ITIMs: striking a balance during cell regulation

Functional immune responses evolve through an exquisitely controlled process integrating signals from activating and inhibitory receptors on the immune cell surface. These complex interactions, which regulate both the quality and magnitude of the ultimate response, depend crucially on two short, loosely conserved motifs found in the intracellular domain of various signaling proteins. These motifs, termed “ITAMs” and “ITIMs” for immunoreceptor tyrosine-based activation (or inhibititory) motifs, provide the basis for two opposed signaling modules that duel for control of cellular activation within the immune system. Well over a decade ago it was observed that the subunits associated with the B cell and T cell antigen