Ligands for natural killer cell receptors: redundancy or specificity

Abstract

Summary: Several inhibitory and activating receptors involved in natural killer cell activation have been characterized. The increasing knowledge about their ligands, including classical MHC class I molecules, non‐classical MHC class I molecules and MHC class I‐related molecules, is shedding new light on the targets of innate immune recognition. While classical MHC class I molecules are constitutively expressed, some MHC class I‐related (MIC) molecules, however, are stress‐induced by ill‐defined stimuli. Two families of ligands for the human activating NKG2D receptor have been identified. These are the MIC proteins encoded by two highly polymorphic genes within the MHC class I and the retinoic acid‐inducible early gene‐1‐like (also designated UL16‐binding) proteins encoded by genes outside the MHC. For the mouse NKG2D receptor, one family, containing at least five distinct ligands, has been described. A better understanding about how targets signal their distress, which renders them susceptible to natural killer (NK)‐cell attack, will help to define the role of NK cells in antimicrobial and antitumor immunity and transplantation. Supported by NIH grants CA89294 and CA89189