Reflections on Self: Self-Serving Signals

This week's issue of Science presents a special section on the concept of self-descrimination entitled Reflections on Self: Immunity and Beyond. At a general level, the concept of "self" can be viewed in many diverse ways, ranging from the philosophical self [me, myself, and I; see the Viewpoint by Churchland ( )], the sociological self [identity within a community; see the Viewpoint by Queller and Strassmann ( )], and the ethical self [as it pertains to scientific issues, such as cloning; see the Viewpoint by Brock ( )], to the immunological self and the many fundamental processes of the immune system that are constantly surveying for signs of nonself that might signal and infection [see Viewpoints by Medzhitov and Janeway ( ) and by Matzinger ( )]. What is surprisingly common to some of these areas is that the concept of self has co-evolved with experimental discoveries that have offered breakthroughs in cell signaling. New hypotheses regarding higher biological functions in the context of self and nonself have arisen from new knowledge of signaling pathways and networks, in disciplines from brain and behavioral neuroscience to immunology. The immune system is the quintessential self and nonself recognition system in biology. In fact, Medzhitov and Janeway explain that the innate immune system of vertebrates can handle foreignness through multiple strategies. These include recognition of nonself or pathogen-associated molecules by specialized cells, recognition of what the authors call "missing self" or removal of cells that don't display proper a self signal, and recognition of "induced self" such as markers of transformed or apoptotic cells. Many of these signaling cascades have been well characterized, and Reviews by O'Neill ( ) and McVicar and Burshtyn ( ) in the STKE Archive describe the evolutionarily conserved Toll-like receptors that function in host defense and the intricate receptor system of the executioner natural killer cells, respectively. A Perspective by Richter and Duckett ( ) in the STKE Archive also discusses IAPs (inhibitors of apoptosis), molecules first identified in viruses able to subvert apoptosis in infected cells. In the Science Viewpoint, Matzinger suggests that the model of tolerating self and attacking nonself is too simplistic today, and proposes that understanding the many layers of immune cells and signals that are called upon from both the adaptive and innate immune systems requires a more network-based model. Indeed, orchestrating such a network requires recruiting the appropriate lymphocytes to locations harboring foreign or modified self-antigens, and in the STKE Review, Bismuth and Boumsell ( ) comment on how semaphorin molecules of the immune system may be critical guidance controls for such encounters. Zell and Jenkins ( ) offer a technique to study T cell receptor-mediated signal transduction ex vivo under conditions that more accurately reflect a T cell's encounter with an antigen-presenting cell. Finally, a Perspective by Rudd et al . ( ) discusses how the T cell co-receptor CTLA-4 may regulate the presence of lipid rafts on the cell surface, thereby controlling T cell activation. Membrane microdomains, such as lipid rafts, are thought to localize signaling molecules that are activated by the T cell receptor. Interestingly, CTLA-4 is also thought to localize at the immunological synapse, the interaface between a T cell and an antigen-presenting cell. More information on lipid rafts, the immunological synapse, and T cell receptor signaling can be found in the STKE Archive of Perspectives, Reviews, and Protocols (see below). You can also explore detailed signaling pathway information at the Connections Maps on T cell signaling by Koretzky and Singer ([http://stke.sciencemag.org/cgi/cm/CMP_7019][1]), B cell signaling by Gauld et al . ([http://stke.sciencemag.org/cgi/cm/CMP_6909][1]), tumor necrosis factor (TNF) signaling by Chen and Goeddel ([http://stke.sciencemag.org/cgi/cm/CMP_7107][1]), and the Jak-STAT pathways by Aaronson and Horvath [Jak-STAT canonical pathway ([http://stke.sciencemag.org/cgi/cm/CMP_8301][1]), Type I interferon pathway ([http://stke.sciencemag.org/cgi/cm/CMP_8390][1]), STAT3 pathway ([http://stke.sciencemag.org/cgi/cm/CMP_9229][1]), and Interferon gamma pathway ([http://stke.sciencemag.org/cgi/cm/CMP_9590][1])]. Featured in This Focus Issue on Self and Nonself Related Resources at STKE [1]: pending:yes