Adaptive immunity, with its rearranging immunoglobulin and T-cell receptors, has caught most of the attention of current immunological research and overshadowed the importance of the receptors expressed by cells of the innate immune system. Natural Killer cells have evolved two main receptor systems to carry out their functions, both of them involving activating and inhibitory receptors, and include members from the Immunoglobulin-like superfamily as well as lectin-like receptors. Killer Immunoglobulin-like receptors (KIR) are polymorphic cell surface molecules present on Natural Killer (NK) cells which recognise classical HLA class I molecules and in doing so provide an alternative means of modulating the immune response to infected or tumoural cells. Lectin-like receptors have been shown to bind to non-classical MHC molecules such as HLA-E and the MHC class I-related chain (MICA). These genetically defined, non-rearranging receptors have recently begun to show the extent of the potential variability encoded within them as well as the complexity of their organisation. NK cell receptors are involved in a great variety of clinical scenarios ranging from resistance/susceptibility to pathogen infections, tumour surveillance, recognition and elimination, and as important elements in solid organ and haematopoietic cell transplant outcome. The functional relationships that exist between the MHC and NK receptors provide a better understanding of the immune responses related to pathogen incursions, malignancies and clinical transplantation.
