Structural immunology and crystallography help immunologists see the immune system in action: How T and NK cells touch their ligands

Abstract

SummaryHost 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 cellsurface 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.

Natural Killer Cell Inhibitory Receptor Expression in Humans and Mice: A Closer Look

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Two Distinct Conformations of a Rinderpest Virus Epitope Presented by Bovine Major Histocompatibility Complex Class I N*01801: a Host Strategy To Present Featured Peptides

“…Analysis of the structures we determined suggests that compared to the structures of other MHC I molecules, including that of bovine N*01301, which was determined recently by Macdonald and colleagues (34), the structure of bovine MHC I N*01801 is distinctive. The structure of bovine N*01801 illuminates a novel presentation strategy for featured epitopes among mammalian MHCs and may lead to improved understanding of the structural basis of CTL-based immune responses (9).…”

Killer Immunoglobulin-like Receptor Genes in Uveitis

“…The KIR interacts with the HLA molecule more from the side than head to head as in the case of the HLA-TCR interaction. 17 Altered function based on antigen specificity, however limited, may play a role in NK surveillance as well as T-cell and antigen-presenting cell interactions, thereby playing a role in antigen-specific autoimmune responses. Multiple cytokines and interleukins are also important in NK cell function or are produced by NK cells, including the recently described IL-17/23 group, which is thought to be important in both autoimmune disease and infections, such as toxoplasmosis, that may be relevant to ocular disease.…”