Natural killer cells: integrating diversity with function

Abstract

The key role of natural killer cells in many aspects of the immune response is now being recognized. The last decade has seen an exponential increase in our understanding of the workings of these cells. Receptor diversity is crucial in allowing natural killer cells to respond effectively to a variety of different pathogens. This article reviews aspects of natural killer cell diversity that combine to generate populations of functional natural killer cells that exist within both the individual and throughout the population at large.

Figure 1

Killer cell immunoglobulin-like receptor (KIR) diversity can impact natural killer (NK) cells at different levels. Schematic diagram of the impact of the areas in which KIR diversity may influence NK cell function. This can occur as the result of differences in gene content and allelic diversity at the KIR locus. This may result in different individuals having different numbers of activating and inhibitory KIR. These KIR are expressed stochastically on NK cells to generate a ‘KIR’ repertoire, which differs among different individuals. The presence or absence of human leucocyte antigen (HLA) class I ligands for these KIR may further impact on this repertoire, and on the functionality of these KIR-expressing subpopulations in different individuals.

Figure 2

Natural killer (NK) cells are diverse at the level of receptors, ligands and signalling adaptors. Examples of the diverse array of molecules that generate diversity in the control of NK cell function are shown. This can occur at the level of the receptor, the ligand or the adaptor molecule. The signalling motifs that control these functions are illustrated: ITIM, immunoreceptor tyrosine-based inhibitory motif; ITAM, immunoreceptor tyrosine-based activating motif; ITSM, immunoreceptor tyrosine-based switch motif and the YINM motif of DAP10.