Structural immunology and crystallography help immunologists see the immune system in action: how T and NK cells...

Host immune system is an important and sophisticated system, maintaining the balance of host response to "foreign" antigens and ignorance to the normal-self. To fulfill this achievement the system manipulates a cell-cell interaction through appropriate interactions between cell-surface receptors and cell-surface ligands, or cell-secreted soluble effector molecules to their ligands/receptors/counter-receptors on the cell surface, triggering further downstream signaling for response effects. T cells and NK cells are important components of the immune system for defending the infections and malignancies and maintaining the proper response against over-reaction to the host. Receptors on the surface of T cells and NK cells include a number of important protein molecules, for example, T cell receptor (TCR), co-receptor CD8 or CD4, co-stimulator CD28, CTLA4, KIR, CD94/NKG2, LILR (ILT/LIR/CD85), Ly49, and so forth. These receptor molecules interact with their ligands on the target cells, including major histocompatibility complex (MHC) (or human leukocyte antigen, HLA), CD80, CD86, and so forth. Detailed understanding of these receptor-ligand pair interactions is crucial for our full knowledge of the immune system, ultimately for us to manipulate the T cell and NK cell functions. Accumulations of the receptor-ligand complex crystal structures in the recent years have provided us a unique angel to see how the immune cells interacting with their partner cells. In this review, we discussed binding specificity, plasticity, and flexibility of the T cell and NK cell receptor/ligand interaction, fitting the structural data with their functions. Structural immunology indeed helps us see how T and NK cells "touch" their target cells in our immune system.