Selection and Adaptation of Cells Expressing Major Histocompatibility Complex Class I–specific Receptors of the Natural Killer Complex

In addition to their essential role in presenting pathogen peptides for recognition by the antigen receptor of killer CD8 T cells, MHC class I molecules can be the targets of another fundamentally different mode of recognition, also involved in fighting pathogens. Studies on NK, a component of the innate immune system that comes into action at the early phase of many intracellular infections, have uncovered an entire set of new receptors for MHC class I that are encoded in the so-called NK gene complex (NKC; 1), and have provided support for the idea that NK cells survey for the absence of self–MHC molecules (2) through these receptors (3). This function is crucial for fighting against certain viruses, such as herpes viruses (4–6). The current challenge that is addressed in this issue of The Journal of Experimental Medicine by Johansson et al.,...