Insights into immune structure, recognition, and signaling

Abstract

In this volume of Immunological Reviews, the articles focus on the structural biology of immunoreceptors and what structure is telling us about function. The issue is unabashedly ‘receptor-centric’ and the proteins covered range from antigen receptors, innate receptors, and cytokine receptors, thereby providing an unusually comprehensive snapshot of the current state of the art in molecular immunology. Of all the major fields in biomedical research, including neurobiology, developmental biology, immunology, microbiology, and genetics, just to name a subset, perhaps structure in the broadest sense has had more of an impact on immunology and played more of a major role in guiding the evolution and maturation of the field than any other. Here, I use the term ‘structure’ to encompass not only direct structural approaches, such as x-ray crystallography and nuclear magnetic resonance spectroscopy (NMR), but also imaging, biophysical, molecular, and mechanistic approaches to interrogate aspects of molecular recognition, oligomerization, and signaling. Perhaps the fact that immunobiology is centered on questions of recognition and discrimination and is largely controlled by receptor-ligand systems has led to an unusually high level of sophistication about structure among immunologists. Personally speaking, having delved into structural questions in neurobiology and developmental biology, I can state without equivocation that the structural and molecular savvy of immunologists has led to greater mechanistic clarity underlying central tenets of the field compared to other disciplines. Dating back to the days of elucidating the first antibody structures and the relation between hypervariable regions and antigen recognition, to the transformative clarity of the first major histocompatibility complex (MHC) structures in explaining MHC restriction, to more recent biophysical and structural investigations of T-cell receptor (TCR) recognition of both classical and non-classical MHC, innate immune receptors such as natural killer (NK) and Toll-like receptors, and cytokine receptors, molecular science has illuminated the path for the experimentalists and assumed a large and highly visible role in immunobiology as a whole.